Cell Biochemistry and Function最新文献

{"title":"Cardiac Glycogen Fluctuations Are Robust in Short-Term Than Long-Term Binge Drinking and Follows a Sex Specific Manner","authors":"Victoria Nelson,&nbsp;Katlyn Heneghan,&nbsp;Daniel Rafferty,&nbsp;Sorab Bedi,&nbsp;Prasanth Puthanveetil","doi":"10.1002/cbf.70135","DOIUrl":"10.1002/cbf.70135","url":null,"abstract":"<div>\u0000 \u0000 <p>Drinking behavior, especially binge drinking, has a debilitating impact on systemic health. In this study, we report that in the absence of any changes in hepatic lactate dehydrogenase activity, the cardiac glycogen level fluctuates following short-term binge drinking. The change in cardiac glycogen levels follows a sex specific pattern. Our work is first to demonstrate that early metabolic changes in the heart, specifically glycogen levels, can be an ideal readout for forthcoming hepatic and systemic complications following binge drinking at an earlier stage. Also, females demonstrate a robust change in cardiac glycogen levels in comparison to their binge drinking male counterparts following short-term exposure, hinting at an early cardiometabolic risk in females. This study prompts us to look at early metabolic changes in the heart as a marker for binge drinking-mediated injury.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145387446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antioxidant Defenses in the Kidneys and Heart of the Freshwater Fish Astyanax lacustris Subjected to High (31°C) and Low (15°C) Temperatures","authors":"Ana Paula Nascimento Corrêa,&nbsp;Luiz Neves Neto,&nbsp;Maria Rosa Dmengeon Pedreiro de Souza,&nbsp;Niumaique Gonçalves da Silva,&nbsp;Jonathan Ratko,&nbsp;Ananda Karla Alves Neundorf,&nbsp;Ieda Cristina Schleger,&nbsp;Tatiana Herrerias,&nbsp;Lucélia Donatti","doi":"10.1002/cbf.70133","DOIUrl":"10.1002/cbf.70133","url":null,"abstract":"<p>Aquatic ecosystems have their abiotic and biotic factors constantly altered by various factors. Among them, water temperature is an abiotic factor that can significantly affect fish physiology, increasing energy demand, which can impact homeostasis and survival. Endocrine and metabolic changes and enzymatic modulation are referred to as stress responses, which can lead to oxidative stress, generating negative physiological effects when temperature limits are exceeded. Oxidative stress biomarkers used in combination can highlight the effects of a stressful condition. Here, we seek to understand how the species <i>Astyanax lacustris</i>, which is native to Brazil and has ecological and economic importance, as well as remarkable research potential, responds to changes in water temperature. Thus, we evaluated the effects of high (31°C ± 1°C) and low (15°C ± 1°C) thermal stress on the antioxidant defense system in the heart and kidneys of <i>A. lacustris</i>. Specimens were collected from artificial lakes in União da Vitória (PR) and exposed to different temperatures for periods of 2, 6, 12, 24, 48, 72, or 96 h, with a control group mantained at 23°C ± 1°C. The results indicated that in the heart exposed to 31°C, there was modulation in the biomarkers superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione (GSH), while at 15°C only GPx activity was altered. In the kidneys of fish exposed to 31°C, there was a change in the activity of the biomarkers catalase (CAT), glutathione-S-transferase (GST), and lipid peroxidation (LPO), while at 15°C there was modulation of the glutathione reductase (GR) biomarker and changes in the levels of reactive oxygen species (ROS). Responses to heat stress were organ-specific, influenced by temperature and exposure time. Principal component analysis (PCA) indicated an association of glutathione-dependent biomarkers at high temperatures in the kidneys, while responses in the heart were similar across temperatures. Overall, <i>A. lacustris</i> exhibited distinct antioxidant responses in different tissues under thermal stress, with kidney response being more sensitive to heat, while cardiac responses were less variable across treatments.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12560206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145376361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dulcitol Selectively Inhibits Proliferation and Metastasis Related Markers in Triple-Negative Breast Cancer: Uncovering an Unforeseen Activity","authors":"Betul Yanik,&nbsp;Filiz Bakar-Ates","doi":"10.1002/cbf.70134","DOIUrl":"10.1002/cbf.70134","url":null,"abstract":"<div>\u0000 \u0000 <p>Breast cancer remains the most commonly diagnosed cancer and a leading cause of cancer-related mortality among women worldwide. Despite advancements in treatment, resistance and toxicity issues highlight the urgent need for novel, effective, and safer therapeutic agents. Natural compounds are increasingly explored as promising sources of anticancer candidates due to their structural diversity and bioactivity. Among these, polyols, a class of sugar alcohols, have been reported to influence cancer cell behaviour by modulating oxidative stress, metabolic pathways and apoptosis, though their precise mechanisms and therapeutic potential remain underexplored. In this study, the anticancer potential of dulcitol, a naturally occurring polyol, was investigated in breast cancer cell lines with different molecular profiles. The cytotoxic effects of dulcitol were assessed using the MTT assay in MCF-7 (ER-positive), MDA-MB-231 (triple-negative), and MCF-10A (non-tumorigenic) breast cell lines. Mechanistic studies including flow cytometry-based cell cycle analysis, apoptosis detection (Annexin V-FITC), mitochondrial membrane potential assessment, caspase activation, and DNA damage analysis were performed on MDA-MB-231 cells. The expression levels of MMP-2 and MMP-9 genes were also evaluated using qRT-PCR. Dulcitol exhibited selective cytotoxicity against MDA-MB-231 cells at concentrations ≥ 7.5 mmol/L, while showing no significant effects on MCF-7 and MCF-10A cells. In MDA-MB-231 cells, dulcitol induced G0/G1 phase cell cycle arrest and promoted apoptosis in a dose-dependent manner. Additionally, increased caspase activity and mitochondrial depolarization were observed, indicating activation of the intrinsic apoptotic pathway. No significant DNA damage was detected; however, a significant downregulation of MMP-2 and MMP-9 expression suggested potential antimetastatic activity. Although the effective in vitro concentrations were relatively high, it should be noted that such levels are commonly required to reveal mechanistic effects in cell-based systems, and pharmacokinetic data on dulcitol are currently unavailable. Therefore, the present findings should be regarded as exploratory and hypothesis-generating, emphasizing the need for in vivo pharmacokinetic and efficacy studies to evaluate translational feasibility. In conclusion, our findings demonstrate that dulcitol selectively targets triple-negative breast cancer cells without affecting normal or ER-positive breast cells. Its ability to induce apoptosis and suppress metastatic gene expression highlights its promise as a potential natural therapeutic candidate for aggressive breast cancer subtypes.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145376288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protease-Activated Receptor 2 Activation Provokes an Increase in Intracellular Calcium and Serotonin Secretion in a Human Enteroendocrine Cell Line","authors":"Beatrix Pfanzagl,&nbsp;Erika Jensen-Jarolim","doi":"10.1002/cbf.70132","DOIUrl":"https://doi.org/10.1002/cbf.70132","url":null,"abstract":"<p>The P-STS human ileal enteroendocrine tumor cell line responds with an increase in intracellular calcium and serotonin secretion to acetylcholine and histamine. Here we show that the cells react similarly to the protease-activated receptor 2 (PAR2) agonists trypsin and SLIGRL-NH2 peptide. The calcium increase induced by both agonists is inhibited by the PAR2 antagonist I-191. PAR2-IN-1, another PAR2 antagonist, did not inhibit the response to the agonist peptide. Trypsin can also be looked upon as a surrogate for mast cell tryptase which cleaves PAR2 at the same site as trypsin. As mast cells may secrete tryptase simultaneously with histamine in close proximity to enteroendocrine cells, we tested whether trypsin and histamine might induce mutual desensitization. Histamine did not desensitize the response to trypsin and trypsin did not desensitize the response to histamine or acetylcholine. Further known effects of short-time incubation with trypsin, namely phosphorylation of p38 mitogen-activated protein kinase and activation of the nuclear factor κB pathway, were not detected in P-STS cells. In conclusion, our findings indicate that serotonin secretion by enterochromaffin cells in response to PAR2 activation might contribute to gastrointestinal symptoms after mast cell activation by food allergens or irritable bowel syndrome. Our data suggest that histamine and mast cell tryptase may have at least additive effects on serotonin secretion.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 11","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RETRACTION: Autophagy Induction by Xanthoangelol Exhibits Anti-Metastatic Activities in Hepatocellular Carcinoma","authors":"","doi":"10.1002/cbf.70131","DOIUrl":"10.1002/cbf.70131","url":null,"abstract":"<p><b>RETRACTION:</b> X. Yang, J. Xie, X. Liu, Z. Li, K. Fang, L. Zhang, M. Han, Z. Zhang, Z. Gong, X. Lin, X. Shi, H. Gao and K. Lu, “Autophagy Induction by Xanthoangelol Exhibits Anti-Metastatic Activities in Hepatocellular Carcinoma,” <i>Cell Biochemistry &amp; Function</i> 37, no. 3 (2019): 128–138, https://doi.org/10.1002/cbf.3374.</p><p>The above article, published online on 18 March 2019 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Robert Heath; and John Wiley &amp; Sons Ltd. The retraction has been agreed upon following concerns raised by third parties. An investigation into these concerns revealed that several elements from Figures 1E, 2C, 3C and 4A were duplicated in other articles. Some of these elements were used to represent different scientific contexts. Additionally, the p62 bands shown for the Hep3B and Huh7 cell lines in Figure 2C were found to be duplicated. The authors were invited to respond to the concerns and provide supporting data, but did not respond. The editors therefore consider the results and conclusions of this article invalid. The authors were notified of the retraction but did not provide any comment.</p>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Ferroptosis on the Pathogenesis and Therapy of Hepatocellular Carcinoma","authors":"Xue Wang,&nbsp;Jinhong Wang,&nbsp;Wentong Li,&nbsp;Shanming Sun","doi":"10.1002/cbf.70129","DOIUrl":"10.1002/cbf.70129","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Hepatocellular carcinoma (HCC) is a complicated disease with low survival rate due to frequent recurrence and lack of efficient therapies. Recent investigations have revealed that ferroptosis plays a crucial role in the progression of tumors, such as HCC. Ferroptosis has been quickly gaining attention in the field of liver diseases, as liver is predisposed to oxidative injury and generally. Emerging evidence supports the notion that dysregulated metabolic pathways plays a role in progression of HCC and liver diseases involved in HCC via ferroptosis. Here, we review physiological role of liver in processing iron ion, our current understanding of iron metabolism, characteristics of ferroptosis, and mechanisms that regulate ferroptosis. In addition, we summarize the role of ferroptosis in the pathogenesis of HCC, including chronic viral hepatitis, nonalcoholic steatohepatitis, alcoholic liver disease, and liver cirrhosis. Finally, we discuss the therapeutic potential of targeting ferroptosis for managing HCC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Summary</h3>\u0000 \u0000 <div>\u0000 \u0000 <ul>\u0000 \u0000 <li>\u0000 <p>Emerging evidence supports the notion that dysregulated metabolic pathways and impaired iron homeostasis play a role in progression of HCC and liver diseases that are involved in HCC via ferroptosis.</p>\u0000 </li>\u0000 \u0000 <li>\u0000 <p>Here, we review physiological role of liver in processing iron ion and summarize the role of ferroptosis in pathogenesis of HCC.</p>\u0000 </li>\u0000 </ul>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging Pathogens: Epstein-Barr Virus and Helicobacter pylori in Gastric Cancer Stem Cell Regulation","authors":"Harshita Shrivastava,&nbsp;Meenakshi Kandpal,&nbsp;Dharmendra Kashyap,&nbsp;Rajan Kumar Pandey,&nbsp;Amit Kumar Dixit,&nbsp;Hem Chandra Jha","doi":"10.1002/cbf.70130","DOIUrl":"https://doi.org/10.1002/cbf.70130","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Gastric cancer remains the primary cause of cancer-related deaths worldwide, where gastric cancer stem cells play an essential role in tumor growth and resistance to various gastric cancer therapies. Emerging evidence suggests that the interaction between Epstein-Barr virus and <i>Helicobacter pylori</i> may affect the regulation of gastric cancer stem cells, although the exact mechanism remains to be explored. This mini-review aims to explore the potential interaction between Epstein-Barr virus and <i>Helicobacter pylori</i> in modifying the characteristics of gastric cancer stem cells, emphasizing their respective roles in the inflammatory tumor microenvironment and the synergistic effects on gastric carcinogenesis. This review article presents the impact of Epstein-Barr virus-induced immune evasion and <i>Helicobacter pylori</i>-induced gastric inflammation on the maintenance and differentiation of gastric cancer stem cells. We seek alterations in numerous signaling pathways related to stemness induced by microbial factors. Based on current understanding, several crucial signaling pathways, including the Notch, Hippo pathway, Nuclear factor-κB, wingless-related integration site, and autophagy pathways, have been found to be implicated in Epstein-Barr virus- and <i>Helicobacter pylori-induced</i> gastric cancer stem cells. Understanding this interplay may reveal novel treatment targets for gastric cancer, particularly in patients with chronic infection by these two pathogens. Further research is needed to clarify the mechanistic interactions driving the synergy between Epstein-Barr virus and <i>Helicobacter pylori</i>, which alters the biology of gastric cancer stem cells. This may provide further insights into early diagnosis and treatment approaches for gastric cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145317767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting Spatiotemporal Heterogeneity of Senescence Markers p16/p21 Across Tissues During Type 2 Diabetes Progression","authors":"Jiayu Yan,&nbsp;Zimei Yi,&nbsp;Siyi Chen,&nbsp;Ruowen Zhao,&nbsp;Jiaying Shi,&nbsp;Shuwen Ding,&nbsp;Jiayu Zhu,&nbsp;Junhua Wu","doi":"10.1002/cbf.70127","DOIUrl":"10.1002/cbf.70127","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigates p16/p21 senescence marker heterogeneity in diabetes-related tissues using the p21-3MR mouse model, focusing on p16 and p21 as senescence markers. Type 2 diabetes, a common age-related disease, impacts multiple organs; the study examines the heterogeneous distribution of senescence markers in tissues including the pancreas, kidney, heart, adipose tissue, femur, spleen, thymus, liver, and lungs. The results reveal significant spatiotemporal heterogeneity in p16/p21 co-expression patterns across different organs during diabetes progression, with varying responses to senescent cell clearance treatments. Specifically, the combination of dasatinib and quercetin demonstrated superior reduction in p16/p21 dual-positive cells in several tissues compared to p21 intervention alone, while p21 intervention showed distinct effects on marker expression in adipose tissue and bone marrow. Immune organs displayed heterogeneity in p16-associated immunosenescence, and the liver and lungs showed greater p16/p21 expression in vascular niches. This is the first study to use the p21-3MR model to explore p16/p21 marker heterogeneity and differential clearance efficacy of senolytic treatments in diabetic tissues. The findings highlight the need for tissue-specific senolytic strategies, particularly targeting adipocytes and metabolic disorders. Future research should focus on understanding the mechanisms of p21^high cell persistence, offering insights for more senescence-targeted treatments.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of the In Vitro Cytotoxic Activities of Several Coumarin Derivatives on Neuroblastoma Cell Lines With In Silico Inhibitory Effects on CDK9, VEGFR2 and EGFR Proteins and ADME Studies","authors":"Fatih Caglar Celikezen,&nbsp;Kamuran Sarac,&nbsp;Ercan Seyhan,&nbsp;Mehmet Enes Aslan,&nbsp;Sena Oner,&nbsp;Hasan Turkez","doi":"10.1002/cbf.70128","DOIUrl":"10.1002/cbf.70128","url":null,"abstract":"<div>\u0000 \u0000 <p>Due to their stable nature and medical applicability properties, coumarin derivatives have fascinated medicinal chemists in the discovery of novel therapeutics. In this study, the cytotoxic/anticancer properties of some newly synthesized coumarin derivatives were aimed at designing, synthesizing, and examining cultured human neuroblastoma cells. Moreover, molecular docking studies were carried out to determine the potential mechanism. In addition, ADMET properties were evaluated to examine the drug-likeness of newly designed coumarin derivatives. To detect the cytotoxic action of compounds, 3-(4,5-dimethylthiazol-2-yl)-2,5 2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release assays were carried out. In addition, Hoechst 33258 staining was used to detect abnormal nuclear structures. In silico, the estimates for all compounds (3a-3c) used in the study revealed that they possessed desirable physicochemical properties for bioavailability. The results of our study showed that all tested compounds exhibited remarkable cytotoxic effects on human neuroblastoma cell lines (<i>p</i> &lt; 0.05). Additionally, among the compounds tested, <b>3a</b> and <b>3c</b> showed selective effects on neuroblastoma cells effectively at all tested concentrations. However, it was found that the selective feature of <b>3b</b>, unlike the others, was concentration-dependent. Our findings clearly showed that novel coumarin derivatives exerted potent and selective anticancer effects. Results of molecular docking studies were in parallel with in vitro studies. Unlike the majority of hybrid coumarin derivatives reported in anticancer research, the present study introduces minimalist, heteroatom-free coumarins bearing bulky aliphatic substituents. These compounds demonstrated selective cytotoxicity against SH-SY5Y neuroblastoma cells and a favorable multi-target binding profile, highlighting a distinct hydrophobic volume-based SAR. As a result, the obtained data exhibited that all used molecules may be good multitarget drug alternatives for the treatment of neuroblastoma.</p></div>","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145238176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of the Hypothalamus-Hypophysis-Adrenal Axis in Male Rats Programmed by Gestational Protein Restriction","authors":"Vinicius Schiavinatto Mariano,&nbsp;José Antonio Rocha Gontijo,&nbsp;Patrícia Aline Boer","doi":"10.1002/cbf.70123","DOIUrl":"https://doi.org/10.1002/cbf.70123","url":null,"abstract":"&lt;p&gt;Diet manipulations during the gestation of animal models, in this case, the lipoprotein diet, mimic the alterations related to low birth weight, providing studies of the mechanisms involved in chronic disease development in later life. Our research group identified in adult male rats submitted to gestational protein restriction, increased anxiety-like behavior, basal plasmatic corticosterone (CORT) and catecholamines elevation, and decrease of hippocampal glucocorticoid receptors (GRs), indicating dysfunction of the stress response, which is related to the sympathetic-adrenomedullary system and the hypothalamic–pituitary–adrenal (HPA) axis alterations. Not only insults during gestation but also maternal care behavior during breastfeeding can modulate the HPA axis of the offspring, influencing its activity in adulthood. Thus, we evaluated maternal care behavior and morphological and functional parameters of the adrenal and pituitary glands in gestational protein-restricted male rats to elucidate mechanisms that can trigger these possible alterations. Mated Wistar rats were submitted to a normal-protein diet (NP group; 17% protein) or a low-protein diet (LP group; 6% protein) throughout pregnancy. From the day of birth until weaning, the maternal care behavior parameters were evaluated, and at the 16th week of age, plasma, adrenal, and pituitary glands were collected for hormonal analysis by LC-MS/MS, western blot, and immunohistochemistry. LP offspring animals showed low birth weight and recovered at weaning, indicating the effect of catch-up growth. No difference in maternal care behavior was found between the groups, suggesting that maternal care may not influence the decrease of hippocampal GR in LP offspring. The plasma levels of 11-dehydrocorticosterone (11-DHC) in 21PND and 16-week-old LP offspring decreased, whereas the plasma levels of CORT and 11-DHC of 8-week-old LP offspring increased. GR and mineralocorticoid receptors, essential to glucocorticoids' practical actions, were increased in the pituitary and adrenal glands in LP 16-week-old animals, indicating possible negative feedback. However, the 98.8% increase in CRH receptor and 63.3% ACTH in the pituitary of the LP offspring indicates failure of this feedback at the pituitary level. The morphometric analysis of the LP 16-week-old animal's adrenal gland showed an increase in medullary area, accompanied by an increase of 39.67% in NeuN, indicating an increase in medullary cellularity and an increase of 168.77% in PCNA, suggesting a cell proliferation under the demand of adrenal hyperactivity. In addition, an increase of 5-HT1A receptor (48.69%) in the LP adrenal gland, which is associated with inhibitory catecholamine secretion, and an increase of immunostaining of 5-HT1A and 5-HT2A receptors differently within the pituitary lobes, suggesting modulation of the HPA axis at the pituitary level through the serotonergic innervation from hypothalamic CRH neurons. Gestation protein restri","PeriodicalId":9669,"journal":{"name":"Cell Biochemistry and Function","volume":"43 10","pages":""},"PeriodicalIF":2.7,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/cbf.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145224366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}