Cell. Physiol. Biochem. [JOURNAL]
Sun
200 papers
Erratum.
Cell Physiol Biochem · 2023 Aug · PMID 37697980 · Publisher ↗
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High Fat High Sugar Diet Reduces Small Intestinal Secretion by Sex-Dependent Mechanisms.
Miller K, Carpinelli S, Rubin M … +10 more , Ahlert J, Kubinski A, Iten BV, Sy K, Lunt B, Meassick K, Ames S, Smith E, Aubin CRS, Al-Nakkash L
Cell Physiol Biochem · 2023 Sep · PMID 37661817 · Publisher ↗
BACKGROUND/AIMS: The goal of this study was to determine the influence of high-fat high-sugar diet (Western diet) on intestinal function and subsequently to determine if there were any beneficial effects of exercise, gen...
BACKGROUND/AIMS: The goal of this study was to determine the influence of high-fat high-sugar diet (Western diet) on intestinal function and subsequently to determine if there were any beneficial effects of exercise, genistein (a naturally occurring phytoestrogen) or both, on the intestine. METHODS: We measured transepithelial short circuit current (I), across freshly isolated segments of jejunum from male and female C57Bl/6J mice randomly assigned to one of the following groups for the 12-week study duration: high-fat high-sugar diet (HFS), HFS with genistein (Gen), HFS with exercise (Ex), or HFS with both genistein and exercise (Gen+Ex) and compared them to lean controls. Genistein concentration was 600 mg genistein/kg diet. Exercise comprised of moderate intensity treadmill running (150 min per week). At the completion of the study, segments of jejunum were frozen for western blot determination of key proteins involved in secretory and absorptive functions, as well as senescence. Intestinal morphology was assessed. Serum cytokine assays were performed. RESULTS: Basal I was significantly decreased (by 70%, P<0.05) in HFS females and males versus leans. This decrease was partially mitigated by exercise in both sexes. In females, the HFS-induced decrease in I was attributed to a significant loss of CLC2, NKCC1 and CFTR expression whereas in males this was due to a significant loss of Na/K-ATPase, K and NKCC1 expression (indicating sex-dependent mechanisms). Exercise mitigated most of the loss of I in both sexes. Our data suggested that A2BR levels were dysregulated in HFS fed mice and that concomitant treatment with Gen or Gen+Ex prevented this disruption in females only. Inflammatory state was associated with body weight changes. CONCLUSION: Our data suggests that the reduced basal jejunal I in HFS mice is attributed to sex-dependent mechanisms and while exercise partially mitigated this, it's mechanism of action was unclear. Improved understanding of Western diet induced intestinal dysfunctions may allow for the development of novel drug targets to treat gastrointestinal disturbances in diabetic obesity.
Kynurenic Acid Levels and Kynurenine Aminotransferase I, II and III Activities in Ganglia, Heart and Liver of Snail Helix Pomatia.
Kronsteiner C, Baran H, Kepplinger B
Cell Physiol Biochem · 2023 Aug · PMID 37597169 · Publisher ↗
BACKGROUND/AIMS: Kynurenic acid (KYNA), a tryptophan metabolite along the kynurenine pathway, is an endogenous antagonist of glutamate ionotropic excitatory amino acid (EAA) receptors and the α7 nicotinic acetylcholine r...
BACKGROUND/AIMS: Kynurenic acid (KYNA), a tryptophan metabolite along the kynurenine pathway, is an endogenous antagonist of glutamate ionotropic excitatory amino acid (EAA) receptors and the α7 nicotinic acetylcholine receptor (nAChR). The involvement of KYNA in various pathological conditions and during the aging process is significant. KYNA synthesis from L-kynurenine (L-KYN), through the action of several kynurenine aminotransferases (KATs), is present in the central nervous system (CNS) and periphery of mammals. We were interested in investigating the ability of the brain and peripheral organs of Helix pomatia snails to synthesize KYNA, in an in vitro study. In comparative studies between rat and snail, we looked for the synthesis of KYNA in the liver. We then looked for an effect of age on KYNA synthesis. METHODS: Ten shell parameters of the Helix pomatia snail were used to establish an Age Rating Scale (ARS), i.e. body weight, shell weight, shell length, width and height, shell opening length and width, lip width, number of shell turns and external shell growth rings. An age of the snails was determined according to the ARS and the snails were divided into three groups, i.e. young, middle and old age. Homogenates of dissected regions, i.e. cerebral ganglia (CG), subpharyngeal ganglia (SG) consisting of pedal, visceral and pleural ganglia, heart and liver, were examined. KYNA was measured by high performance liquid chromatography (HPLC) and KAT activities were measured by an enzymatic method. RESULTS: With respect to ARS, an evaluation of the age of the snails between young (1-2 years), middle (5-7 years) and old (9-13 years) showed significant differences (p<0.001). Analysis of KYNA levels in different snail tissues, i.e. CG, SG, heart and liver, showed an occurrence in the low femtomolar range. Marked and significant increases of KYNA were found in the liver of middle and old age groups. In the SG, KYNA decreased significantly with age. There were no differences in KYNA levels between groups in CG and heart. The lowest KAT activity was found in CG and SG (5 pmol/mg/h), while in heart and liver the values were visibly higher (between 8 and 80 pmol/mg/h). Only in the liver, and exceptionally only for KAT I, the activity increased significantly with age, i.e. up to 14 years. No age-related changes in KAT I, II and III activities were found in CG and SG. Snail liver shows a different pattern of KAT activities compared to the rat liver. CONCLUSION: Regions of the CNS and periphery of the snail Helix pomatia are able to synthesize KYNA due to KAT activities. In the snail liver, KAT I activity increased with age. Notably, there was no age-related increase in KAT activities in the heart and especially in the CNS of Helix pomatia, indicating significant differences from mammals. A moderate KYNA metabolism in the Helix pomatia snail in the periods studied, up to 14 years, could be a physiological phenomenon that protects organs from possible functional insufficiency due to high KYNA levels, as has been suggested. It is reasonable to search for the factor(s) that could regulate the concentration of KYNA in the body of the snail.
A High-Fat Diet Induces Cardiac Damage in Obesity-Resistant Rodents with Reduction in Metabolic Health.
Cardoso JC, Martins VVP, Madureira AR … +6 more , Sales ST, Filetti FM, Corrêa CR, Nogueira BV, Lima-Leopoldo AP, Leopoldo AS
Cell Physiol Biochem · 2023 Aug · PMID 37590499 · Publisher ↗
BACKGROUND/AIMS: Obesity resistance is associated with the complex interaction of stringent and environmental factors that confer the ability to resist mass gain and body fat deposition, even when eating high-calorie die...
BACKGROUND/AIMS: Obesity resistance is associated with the complex interaction of stringent and environmental factors that confer the ability to resist mass gain and body fat deposition, even when eating high-calorie diets. Considering that there are numerous gaps in the literature on the metabolic processes that explain Obesity resistance, specifically in relation to oxidative stress, the purpose of the study was to investigate whether obesity-resistant (OR) rats develop elevated reactive oxygen species in cardiac tissue. METHODS: Wistar rats were initially randomized into two groups: a standard diet (SD) and a high-fat diet (HFD) group. The SD and HFD groups were further divided into control (C), OR, and obese prone (OP) subgroups based on body weight. This criterion consisted of organizing the animals in each group in ascending order according to body weight (BW), and the cutoff point was identified in the animals by terciles: 1) lower BW; 2) intermediate BW; and 3) higher BW. Rats were sacrificed on the 14th week, and serum and organs were collected. Nutritional assessment, food profiles, histological analysis, comorbidities, and cardiovascular characteristics were determined. RESULTS: BW showed a significant difference between the standard diet and high-fat diet groups in the 4th week of the experimental protocol, characterizing obesity. In the 4th week, after the characterization of Obesity resistance, there was a significant difference in BW between groups C, OP, and OR. The OP and OR groups showed a significant increase in caloric intake in relation to the C group. The OP group showed a significant increase in final BW, retroperitoneal fat pad mass, sum of corporal fat deposits and reactive oxygen species, in relation to groups C and OR. The area under the glycemic curve, insulin resistance index and basal glucose were elevated in the OP group in relation to the C. OP also promoted an increase in HOMA-IR when compared with C. OR rats showed a non-significant increase in insulin and HOMA-IR in OR vs. C (p = ~0.1), but no significant differences were observed between OP vs. OR for these parameters, suggesting that both groups suffered from decreased metabolic health. Total cardiac mass, left ventricular cross-sectional area, and cholesterol levels were significantly elevated in the OP and OR groups compared with the C group. CONCLUSION: A high-fat diet induces cardiac damage in obesity-resistant rodents with reduction in metabolic health.
The Absence of an Na/CaExchanger (NCX) in Bullfrog Proximal Tubules and Cellular pH is More Influential Than Cellular Ca on Proximal Na Transport.
Matsumura Y
Cell Physiol Biochem · 2023 Jul · PMID 37522756 · Publisher ↗
BACKGROUND/AIMS: The functional significance of the Na/Ca exchanger (NCX) in basolateral membranes in the proximal tubule remains controversial. The key factor in crosstalk between the apical and basolateral sides is not...
BACKGROUND/AIMS: The functional significance of the Na/Ca exchanger (NCX) in basolateral membranes in the proximal tubule remains controversial. The key factor in crosstalk between the apical and basolateral sides is not known. METHODS: We investigated the basolateral membranes, using double-barreled Ca or pH ion-selective microelectrodes. We used doubly perfused bullfrog kidneys in vivo, and switched the basolateral solution (renal portal vein) to experimental solutions. RESULTS: In the control, cellular pH (pH) was 7.33 ± 0.032 (mean ± SE, n = 7) and in separate experiments, cellular Ca activity (aCa) was 249.6 ± 35.54 nM (n = 28). Changing to respiratory acidosis, pH was significantly acidified by 0.123 pH units on average and the change of aCa was +53.1 nM (n = 9 ns). In metabolic acidosis, pH was reduced by 0.151 while aCa was reduced by 143.4. Using the 30 mM K solution, pH was increased by 0.233 while aCa was reduced by 203.9, with depolarization. Both ionomycin and ouabain caused aCa to increase. In the 0.5 mM Na solution (replaced with BIDAC Cl), pH was reduced by 0.177. No changes in aCa (+49.8 ns) were observed although we recorded depolarization of 15.2 mV. In the 0.5 mM Na solution, replaced with raffinose, no changes in aCa (-126.4 ns) were observed with depolarization (6.5 ns). CONCLUSION: Our results suggest that thermodynamic calculations of cellular Na concentration led to the conclusion that either a Na/HCO exchanger (NBC) or NCX could be present in the same basolateral membrane. H ions are the most plausible key factor in the crosstalk.
De Novo Cloning and Functional Characterization of a Mechanosensitive Piezo-Like Ion Channel in the Crayfish.
Ergin B, Saglam B, Arslan K … +4 more , Coskun Beyatli N, Taskiran ZE, Bastug T, Purali N
Cell Physiol Biochem · 2023 Jul · PMID 37515574 · Publisher ↗
BACKGROUND/AIMS: Mechanosensitive ion channels are the principal elements in the transduction of mechanical force to neural activity. To date, considerably fewer studies have been published about the molecular and struct...
BACKGROUND/AIMS: Mechanosensitive ion channels are the principal elements in the transduction of mechanical force to neural activity. To date, considerably fewer studies have been published about the molecular and structural properties of mechanosensitive channels. Piezo channels are the only ion channel family in eukaryotes which is selectively gated by the membrane tension. Piezo channels have been described in mammals and some other eukaryotes. However, not much information is available for the crustaceans. METHODS: Conventional cloning methods were used to clone the putative PIEZO channel mRNA in crayfish ganglia samples. HEK293T cells were transfected by the plasmid of the cloned gene for functional studies. The CDS of the mRNA translated into the protein sequence and three-dimensional structure of the channel has been calculated. RESULTS: An mRNA, 9378 bp, was firstly cloned from crayfish which codes a 2674 residues protein. The cloned sequence is similar to the piezo channel mRNAs reported in the other species. The sequence of the coded protein has been analyzed, and some functional domains have been identified. A three-dimensional structure of the coded protein was successfully calculated in reference to mouse piezo 1 channel protein data. A plasmid with a fluorescent protein indicator was synthesized for heterologous expression in HEK293T cells. The evoked calcium response to mechanical stimulation was not different from those observed in the control cells. However, the transfected cells were more sensitive to the gating modifier YODA-1. CONCLUSION: Based on the apparent similarity in sequence, structure and functional properties to other known piezo channels, it has been proposed that cloned mRNA may code a piezo-like ion channel in crayfish.
Unprecedentedly High Level of Intracellular Vitamin C and DNA Epigenetic Marks in Prostate: Relevant for Male Fertility?
Guz J, Zarakowska E, Mijewski P … +7 more , Wasilow A, Szpotan J, Foksinski M, Brzoszczyk B, Gackowski D, Jarzemski P, Olinski R
Cell Physiol Biochem · 2023 Jun · PMID 37463420 · Publisher ↗
BACKGROUND/AIMS: Seminal plasma composition is affected by the physiological state of the prostate, the major male reproductive gland. Semen components, like vitamin C, can modulate sperm function. Vitamin C is an effect...
BACKGROUND/AIMS: Seminal plasma composition is affected by the physiological state of the prostate, the major male reproductive gland. Semen components, like vitamin C, can modulate sperm function. Vitamin C is an effective scavenger of free radicals and is an essential component of enzymes such as TET proteins involved in the DNA demethylation process. In the present study, a broad range of parameters which may influence the metabolic state of the prostate gland were analysed including blood and prostate tissue vitamin C, epigenetic DNA modifications and 8-oxo-7,8-dihydro-2'-deoxyguanosine in DNA of leukocytes and prostate tissues. METHODS: The experimental material were tissue samples from patients with benign prostatic hyperplasia (BPH), normal/marginal prostate tissues from prostate cancer patients, leukocytes from healthy donors, and blood plasma from BPH patients and healthy donors. We applied ultra-performance liquid chromatography methods with mass spectrometry and/or UV detection. RESULTS: We found an unprecedentedly high level of intracellular vitamin C in all analysed prostatic tissues (benign prostatic hyperplasia and normal, marginal ones), a value much higher than in leukocytes and most human tissues. DNA epigenetic patterns in prostate cells are similar to other soft tissues like the colon, however, its uniqueness is the unprecedentedly high level of 5-(hydroxymethyl)-2'-deoxyuridine and a significant increase in 5-formyl-2'-deoxycytidine value compared to aforementioned tissues. Moreover, the level of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an established marker of oxidative stress, is significantly higher in prostate tissues than in leukocytes and many previously studied soft tissues. CONCLUSION: Our results pointed out that prostatic vitamin C (regarded as the main supplier of the vitamin C to seminal plasma) and the DNA modifications (which may be linked to the regeneration of prostate epithelium) may play important role to maintain the prostate health.
Autophagy Inhibition Increased Sensitivity of Pancreatic Cancer Cells to Carbon Ion Radiotherapy.
Sudo M, Tsutsui H, Hayashi S … +11 more , Yasuda K, Mitani K, Iwami N, Anzai M, Tsubouchi T, Ishida M, Satoi S, Kanai T, Hirono S, Hatano E, Fujimoto J
Cell Physiol Biochem · 2023 Jul · PMID 37463410 · Publisher ↗
BACKGROUND/AIMS: Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer. METHODS: We performed carbon ion radiotherap...
BACKGROUND/AIMS: Pancreatic cancer has the poorest survival rate among all cancer types. Therefore, it is essential to develop an effective treatment strategy for this cancer. METHODS: We performed carbon ion radiotherapy (CIRT) in human pancreatic cancer cell lines and analyzed their survival, apoptosis, necrosis, and autophagy. To investigate the role of CIRT-induced autophagy, autophagy inhibitors were added to cells prior to CIRT. To evaluate tumor formation, we inoculated CIRT-treated murine pancreatic cancer cells on the flank of syngeneic mice and measured tumor weight. We immunohistochemically measured autophagy levels in surgical sections from patients with pancreatic cancer who received neoadjuvant chemotherapy (NAC) plus CIRT or NAC alone. RESULTS: CIRT reduced the survival fraction of pancreatic cancer cells and induced apoptotic and necrotic alterations, along with autophagy. Preincubation with an autophagy inhibitor accelerated cell death. Mice inoculated with control pancreatic cancer cells developed tumors, while those inoculated with CIRT/autophagy inhibitor-treated cells showed significant evasion. Surgical specimens of NAC-treated patients expressed autophagy comparable to control patients, while those in the NAC plus CIRT group expressed little autophagy and nuclear staining. CONCLUSION: CIRT effectively killed the pancreatic cancer cells by inhibiting their autophagy-inducing abilities.
Role of O-GlcNAcylation in Breast Cancer Biology.
Kozal K, Krześlak A
Cell Physiol Biochem · 2023 Jun · PMID 37302012 · Publisher ↗
Breast cancer is the most common type of cancer in women. It has been extensively researched over the past decades, but the underlying mechanisms of its growth, proliferation, invasion, and metastasis require further inv...
Breast cancer is the most common type of cancer in women. It has been extensively researched over the past decades, but the underlying mechanisms of its growth, proliferation, invasion, and metastasis require further investigation. Dysregulation of O-GlcNAcylation which is one of the most abundant post-translational modifications, impacts on the malignant features of breast cancer. O-GlcNAcylation is broadly recognized as a nutrient sensor and participates in cells' survival and death. Through its involvement in protein synthesis and energy metabolism, especially glucose metabolism, O-GlcNAcylation enables adaptation to a hostile environment. It supports the migration and invasion of cancer cells and may be crucial for breast cancer metastasis. This review summarizes the current state of knowledge about O-GlcNAcylation in breast cancer: the origins of its dysregulation, its effect on the different aspects of breast cancer biology, and the potential utility in diagnostics and therapy.
Role of Nutritional Supplements on Gut-Muscle Axis Across Age: a Mini-Review.
Nucci RAB, Filho VAN, Jacob-Filho W … +2 more , Otoch JP, Pessoa AFM
Cell Physiol Biochem · 2023 May · PMID 37190847 · Publisher ↗
Sarcopenia is a progressive skeletal muscle disorder associated with aging, resulting in loss of muscle mass and function. It has been linked to inflammation, oxidative stress, insulin resistance, hormonal changes (i.e....
Sarcopenia is a progressive skeletal muscle disorder associated with aging, resulting in loss of muscle mass and function. It has been linked to inflammation, oxidative stress, insulin resistance, hormonal changes (i.e. alterations in the levels or activity of hormones which can occur due to a variety of factors, including aging, stress, disease, medication, and environmental factors), and impaired muscle satellite cell activation. The gut microbiome is also essential for muscle health, and supplements such as probiotics, prebiotics, protein, creatine, and betaalanine can support muscle growth and function while also promoting gut health. Chronic low-grade inflammation is a leading cause of sarcopenia, which can activate signaling pathways that lead to muscle wasting and reduce muscle protein synthesis. Insulin resistance, hormonal changes, and impaired muscle satellite cell activation contribute to sarcopenia, and high levels of fat mass also play a role in the pathogenesis of sarcopenia. Resistance exercise and dietary supplementation have been shown to be effective treatments for sarcopenia. In addition, a combination of resistance exercise and supplementation has been shown to have a more significant beneficial effect on anthropometric and muscle function parameters, leading to a decrease in sarcopenic state. Thus, understanding the relationship between the gut microbiome and muscle metabolism is crucial for developing new treatments for sarcopenia across age groups.
The Possible Role of Β-Cell Senescence in the Development of Type 2 Diabetes Mellitus.
Novoselova EG, Lunin SM, Khrenov MO … +3 more , Glushkova OV, Novoselova TV, Parfenyuk SB
Cell Physiol Biochem · 2023 Feb · PMID 37161897 · Publisher ↗
This minireview discusses the very important biomedical problem of treating type 2 diabetes mellitus (T2D). T2D accounts for more than 90% of the total number of diagnosed cases of diabetes mellitus and can result from a...
This minireview discusses the very important biomedical problem of treating type 2 diabetes mellitus (T2D). T2D accounts for more than 90% of the total number of diagnosed cases of diabetes mellitus and can result from aging, inflammation, obesity and β-cell senescence. The main symptom of both T2D and type 1 diabetes (T1D) is an increase in blood glucose concentration. While T1D is insulin-dependent and is associated with the destruction of pancreatic β-cells, T2D does not require lifelong insulin administration. In this case, pancreatic β-cells are not destroyed, but their functional activity is deregulated. In T2D, metabolic stress increases the number of senescent β-cells while impairing glucose tolerance. The potential paracrine effects of senescent β-cells highlight the importance of the β-cell senescenceassociated secretory phenotype (SASP) in driving metabolic dysfunction. We believe that the main reason for the deregulation of the functional activity of pancreatic β-cells in T2D is associated with their "aging" or senescence, which may be induced by various stressors. We propose the use of peroxiredoxin 6 as a new senolytic drug, and the role of β-cell senescence in the development of T2D is discussed in this review.
miRNA-mRNA Network in PBMCs of PCOS Women Identifies Overactivated Stress-Activated Kinases.
Krishna MB, Johnson BS, Vasudevan M … +2 more , Pillai SM, Laloraya M
Cell Physiol Biochem · 2023 Apr · PMID 37125425 · Publisher ↗
BACKGROUND/AIMS: Earlier studies have revealed the miRNAs and mRNAs involved in Polycystic Ovarian Syndrome (PCOS), but little is known about their regulatory networks. METHODS: To address this issue, we applied a compre...
BACKGROUND/AIMS: Earlier studies have revealed the miRNAs and mRNAs involved in Polycystic Ovarian Syndrome (PCOS), but little is known about their regulatory networks. METHODS: To address this issue, we applied a comprehensive miRNA, mRNA profiling approach in peripheral blood of PCOS patients. We identified 30 differential miRNAs and 3310 differential transcripts. A robust computational framework was created to integrate matched miRNA and mRNA expression profiles in PCOS using feed-forward loops. RESULTS: The network consisted of differential miRNAs, transcription factors (TFs), and their common predicted target genes. The key network consisted of 14 non-orphan network clusters with 50 TF-gene pairs, 8 TF-TF pairs, 6 miRNA-TF pairs and 36 miRNA- gene pairs which were later dissected into 16 subclusters. Gene ontology annotations revealed that a host of signals (hormone, growth factors -EGF/ PDGF, thrombopoietin, oxidative stress and vitamin/nutrition) regulate MAPK signaling altering angiogenesis, JAK-STAT signaling, apoptosis, inflammatory and immune response and steroidogenesis in PCOS women. CONCLUSION: MAPK signaling is identified as the syndrome´s major dysregulated pathway. Our data imparts a robust foundation to expand the work and pave the way to focus efforts on p38MAPK targeted therapeutic strategies in PCOS.
Erratum.
Cell Physiol Biochem · 2023 Apr · PMID 37125422 · Publisher ↗
Abstract loading — click title to view on PubMed.
Erratum.
Cell Physiol Biochem · 2023 Apr · PMID 37125421 · Publisher ↗
Abstract loading — click title to view on PubMed.
Expression of Concern.
Cell Physiol Biochem · 2023 Apr · PMID 37125420 · Publisher ↗
Abstract loading — click title to view on PubMed.
Expression of Concern.
Cell Physiol Biochem · 2023 Apr · PMID 37125419 · Publisher ↗
Abstract loading — click title to view on PubMed.
Can Iron and Polyunsaturated Fatty Acid Supplementation Induce Ferroptosis?
Delesderrier E, Monteiro JDC, Freitas S … +3 more , Pinheiro IC, Batista MS, Citelli M
Cell Physiol Biochem · 2023 Apr · PMID 37087689 · Publisher ↗
Ferroptosis is a regulated non-apoptotic cell death process triggered by excessive iron-induced lipid peroxidation. Excess intracellular iron promotes lipid peroxidation by increasing reactive oxygen species formation th...
Ferroptosis is a regulated non-apoptotic cell death process triggered by excessive iron-induced lipid peroxidation. Excess intracellular iron promotes lipid peroxidation by increasing reactive oxygen species formation through the Fenton reaction. Thus, iron and polyunsaturated fatty acid intake may trigger ferroptosis under certain conditions. The aims of this review were to compile and examine evidence in the literature for the effects of iron and polyunsaturated fatty acid supplementation on ferroptosis. Omega-6 polyunsaturated fatty acids have relatively greater susceptibility to lipid peroxidation and could, therefore, participate in ferroptosis. By contrast, omega-3 polyunsaturated fatty acids promote intracellular antioxidants synthesis and reduce the formation of hydroperoxides that induce ferroptosis. As intestinal iron absorption is regulated by iron nutritional status, individuals with normal functioning of the hepcidin-ferroportin axis are at low risk of developing iron overload in response to ingestion of iron-rich foods. Therefore, iron supplementation is potentially toxic mainly for the intestinal epithelium and the microbiota. In animal models, iron-rich diets increased oxidative damage, lowered the glutathione concentration within hepatocytes, and downregulated desaturases that synthesize long-chain polyunsaturated fatty acids. These adverse effects of iron supplementation were prevented by omega-3 fatty acid co-supplementation. The impact of food and supplement intake on ferroptosis has seldom been investigated. Scientific evidence still does not allow us to know for sure whether iron and PUFA supplementation are capable of inducing ferroptosis. As the mechanisms that control ferroptosis can determine whether cells proliferate or die, future studies should directly investigate the effects of nutrient supplementation and food intake on the ferroptosis process in different types of cells and tissues.
Photo-Excited Toluidine Blue Disaggregates the Repeat Tau and Modulates End-Binding Protein EB1, Cytoskeletal Structure in Neuronal Cells.
Chinnathambi S, Dubey T, Chandrashekar M
Cell Physiol Biochem · 2023 Apr · PMID 37074918 · Publisher ↗
BACKGROUND/AIMS: Alzheimer's disease is a progressive neurological disorder characterized by the intracellular accumulation of Tau protein aggregates. In the present work, we studied the effect of Toluidine Blue and phot...
BACKGROUND/AIMS: Alzheimer's disease is a progressive neurological disorder characterized by the intracellular accumulation of Tau protein aggregates. In the present work, we studied the effect of Toluidine Blue and photo-excited Toluidine Blue on the aggregation of repeat Tau using in vitro assays. METHODS: The in vitro experiments were carried out on recombinant repeat Tau which was purified by cation exchange chromatography. The ThS fluorescence analysis was used to study the aggregation kinetics of Tau. CD spectroscopy and electron microscopy were used to study the secondary structure and morphology of Tau respectively. The actin cytoskeleton modulation was studied in Neuro2a cells with help of immunofluorescent microscopy. RESULTS: Results showed that Toluidine Blue efficiently inhibited the formation of higher-order aggregates, which was evidenced by Thioflavin S fluorescence assay, SDS-PAGE, and TEM. Immunofluorescence studies on the cytoskeleton of Neuro2a cells showed that Toluidine Blue and photo-excited Toluidine Blue treatment at a non-toxic concentration of 0.5 µM stimulated the formation of actin-rich lamellipodia and filopodia structures. Tubulin networks were also differentially modulated after the treatment of Toluidine Blue and photo-excited Toluidine Blue. End-binding protein 1 (EB1) levels were observed to increase after Toluidine Blue and photo-excited Toluidine Blue treatment indicating accelerated microtubule polymerization. CONCLUSION: The overall study suggested that Toluidine Blue inhibited the aggregation of soluble Tau and photo-excited Toluidine Blue disaggregated the pre-formed Tau filaments. In our study, TB and PE-TB were observed to be potent against Tau aggregation. We observed a distinctive modulation of actin, tubulin networks, and EB1 levels after TB and PE-TB treatment, which suggested that TB and PE-TB have potency against cytoskeleton deformities.
A High Dose of Calcitriol Inhibits Glycolysis and M2 Macrophage Polarization in the Tumor Microenvironment by Repressing mTOR Activation: in vitro and Molecular Docking Studies.
Munir MT, Halim SA, Santos JM … +7 more , Khan F, Khan A, Rahman MM, Hussain F, Al-Harrasi A, Gollahon LS, Rahman SM
Cell Physiol Biochem · 2023 Apr · PMID 37052042 · Publisher ↗
BACKGROUND/AIMS: Macrophages interact with tumor cells within the tumor microenvironment (TME), which plays a crucial role in tumor progression. Cancer cells also can instruct macrophages to facilitate the spread of canc...
BACKGROUND/AIMS: Macrophages interact with tumor cells within the tumor microenvironment (TME), which plays a crucial role in tumor progression. Cancer cells also can instruct macrophages to facilitate the spread of cancer and the growth of tumors. Thus, modulating macrophages-cancer cells interaction in the TME may be therapeutically beneficial. Although calcitriol (an active form of vitamin D) has anticancer properties, its role in TME is unclear. This study examined the role of calcitriol in the regulation of macrophages and cancer cells in the TME and its influence on the proliferation of breast cancer cells. METHODS: We modeled the TME, in vitro, by collecting conditioned medium from cancer cells (CCM) and macrophages (MCM) and culturing each cell type separately with and without (control) a high-dose (0.5 µM) calcitriol (an active form of vitamin D). An MTT assay was used to examine cell viability. Apoptosis was detected using FITC (fluorescein isothiocyanate) annexin V apoptosis detection kit. Western blotting was used to separate and identify proteins. Quantitative real-time PCR was used to analyze gene expression. Molecular docking studies were performed to evaluate the binding type and interactions of calcitriol to the GLUT1 and mTORC1 ligand-binding sites. RESULTS: Calcitriol treatment suppressed the expression of genes and proteins implicated in glycolysis (GLUT1, HKII, LDHA), promoted cancer cell apoptosis, and reduced viability and Cyclin D1gene expression in MCM-induced breast cancer cells. Additionally, calcitriol treatment suppressed mTOR activation in MCM-induced breast cancer cells. Molecular docking studies further showed efficient binding of calcitriol with GLUT1 and mTORC1. Calcitriol also inhibited CCM-mediated induction of CD206 and increased TNFα gene expression in THP1-derived macrophages. CONCLUSION: The results suggest that calcitriol may impact breast cancer progression by inhibiting glycolysis and M2 macrophage polarization via regulating mTOR activation in the TME and warrants further investigation in vivo.
Biochemical and Biophysical in Vitro Studies and Systematic Literature Review on the Antioxidant and Antiglycation Activities of Trazodone.
Nesterowicz M, Żendzian-Piotrowska M, Ładny JR … +2 more , Zalewska A, Maciejczyk M
Cell Physiol Biochem · 2023 Mar · PMID 36988041 · Publisher ↗
BACKGROUND/AIMS: Trazodone is a selective serotonin reuptake inhibitor; however, other mechanisms of the drug's anti-depressive properties have also been postulated. Hence, the aim of the study was to perform a systemati...
BACKGROUND/AIMS: Trazodone is a selective serotonin reuptake inhibitor; however, other mechanisms of the drug's anti-depressive properties have also been postulated. Hence, the aim of the study was to perform a systematic review and assess antiglycoxidative properties of trazodone in in vitro models. METHODS: Trazodone's scavenging and chelating properties were measured with spectrophotometric method. The impact of the drug on carbonyl/oxidative stress was marked in the bovine serum albumin (BSA) model where sugars (glucose, fructose, galactose, ribose) and aldehydes (glyoxal and methylglyoxal) were used as glycation agents. Aminoguanidine and N-acetylcysteine (NAC) were applied as reference glycation/free radical inhibitors. Glycation biomarkers (kynurenine, N-formylkynurenine, dityrosine as well as advanced glycation end products contents) were assessed spectrofluorometrically. Concentrations of oxidation parameters (total thiols (TTs), protein carbonyls (PCs) and also advanced oxidation protein products (AOPPs) levels) were determined spectrophotometrically. RESULTS: We demonstrated that trazodone poorly scavenged radicals (hydroxyl radical, nitric oxide, hydrogen peroxide and 2,2-diphenyl-1-picrylhydrazyl radical) and showed low ferrous ion chelating, unlike aminoguanidine and NAC. Sugars/aldehydes caused enhancement of glycation parameters, as well as a decrease of TTs and an increase of PCs and AOPPs levels compared to BSA incubated alone. Trazodone did not reduce oxidation parameters to the baseline (BSA) and significantly exacerbated glycation markers in comparison with both BSA and BSA+glycators. The content of glycation products was markedly lower in aminoguanidine and NAC than in trazodone. The molecular docking of trazodone to BSA revealed its very low affinity, which may indicate non-specific binding of trazodone, facilitating the attachment of glycation factors. CONCLUSION: According to our findings, it may be concluded that trazodone poorly counteracts oxidation and intensifies glycation in vitro. A possible mechanism for antiglycoxidative effect of trazodone in vivo may be the enhancement of the body's adaptive response, as indicated by the results of our systematic review.
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