Gabriel Fernandes Teixeira , Juliana Mentzinger , Juliana Arruda de Souza Monnerat , Larissa Lírio Velasco , Bianca Bittencourt Lucchetti , Luiza Rocha , Livia Alves de Oliveira , Renata Frauches Medeiros , Antonio Claudio Lucas da Nóbrega , Helena Naly Miguens Rocha , Natália Galito Rocha
{"title":"Stress in pregnancy alters hepatic unfolded protein responses in male adult offspring","authors":"Gabriel Fernandes Teixeira , Juliana Mentzinger , Juliana Arruda de Souza Monnerat , Larissa Lírio Velasco , Bianca Bittencourt Lucchetti , Luiza Rocha , Livia Alves de Oliveira , Renata Frauches Medeiros , Antonio Claudio Lucas da Nóbrega , Helena Naly Miguens Rocha , Natália Galito Rocha","doi":"10.1016/j.mce.2024.112430","DOIUrl":"10.1016/j.mce.2024.112430","url":null,"abstract":"<div><div>Stress is considered an independent risk factor for the development of cardiometabolic disorders, especially when it occurs during pregnancy, and it may play an important role in stress-induced fetal programming on the protein-folding homeostasis in hepatic endoplasmic reticulum. The study aimed to determine the effects of prenatal stress on the unfolded protein responses in the liver of male and female offspring of Wistar rats. Pregnant Wistar rats at 90 days old were divided into control and stress groups. The unpredictable stress protocol was performed from the 14th to the 21st day of pregnancy. The offspring of each group were divided into four groups according to sex and intervention. After the lactation period, the dams were anesthetized and euthanized for blood collection to determine plasma corticosterone levels. At 90 days old, the offspring were anesthetized and euthanized for liver tissue collection to measure protein expression of the endoplasmic reticulum stress. Dams submitted to prenatal stress showed an increase in corticosterone levels when compared to the control group. In the male offspring, prenatal stress induced lower body mass at birth and at 90 days compared to control, while females presented lower body mass only at birth. Prenatal stress reduced eIF2α expression in males, while increased p-eIF2α expression similarly in both sexes. Furthermore, only males had a greater p-eIF2α/eIF2α ratio and androgen receptor expression when compared to its respective control group and females. Prenatal stress induced a hepatic programming in the reticulum endoplasmic responses only in males at 90 days old by increasing androgen receptor, eIF2α phosphorylation and activity, while in females stress during pregnancy reduced cHDL and had little impact on hepatic unfolded protein response.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"596 ","pages":"Article 112430"},"PeriodicalIF":3.8,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yi Zhang , Ting Pan , Yanting Yang , Xingzhao Xu , Yao Liu
{"title":"Oridonin attenuates diabetic retinopathy progression by suppressing NLRP3 inflammasome pathway","authors":"Yi Zhang , Ting Pan , Yanting Yang , Xingzhao Xu , Yao Liu","doi":"10.1016/j.mce.2024.112419","DOIUrl":"10.1016/j.mce.2024.112419","url":null,"abstract":"<div><div>Oridonin (Ori) possesses anti-inflammatory properties. However, its potential to treat diabetic retinopathy (DR) remains unclear. This study aimed to investigate the retinal protective function of Ori and the underlying mechanism. In streptozotocin-induced mice, Ori alleviated visual impairment, reduced retinal and vascular lesions, protected the neuroretinal structure, reversed retinal nerve layer thickening. Addtionnally, Ori reduced TNF-α and IL-1β levels in the peripheral blood, and suppressed retinal NLRP3 inflammasome-related inflammatory factor. In vitro, human retinal endothelial cells (hRECs) were stimulated by high glucose (HG). HG-stimulated hRECs activated the NLRP3 inflammasome, whereas Ori significantly alleviated pyroptosis by enhancing cell viability and reducing IL-1β levels in the supernatant. Ori also inhibited NF-κB/NLRP3 inflammasome pathway. NEK7 depletion alleviated NLRP3 inflammasome activation and, to some extent, mimicked the role of Ori. Indeed, Ori reversed NLRP3 inflammasome activation by suppressing NEK7–NLRP3 interaction. Therefore, Ori may serve as a potential therapeutic agent for attenuating DR progression.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"596 ","pages":"Article 112419"},"PeriodicalIF":3.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Corrine F. Monaco , Chloe M. Jones , Harlan R. Sayles , Brooke Rudloff , Renee McFee , Andrea S. Cupp , John S. Davis
{"title":"Luteal fibroblasts produce prostaglandins in response to IL1β in a MAPK-mediated manner","authors":"Corrine F. Monaco , Chloe M. Jones , Harlan R. Sayles , Brooke Rudloff , Renee McFee , Andrea S. Cupp , John S. Davis","doi":"10.1016/j.mce.2024.112420","DOIUrl":"10.1016/j.mce.2024.112420","url":null,"abstract":"<div><div>The corpus luteum is a temporary endocrine gland that is crucial for pregnancy, as it produces the progesterone needed to maintain optimal uterine conditions for implantation. In the absence of a conceptus, the corpus luteum becomes non-functional and undergoes rapid tissue remodeling to regress into a fibrotic corpus albicans. Early luteal regression is characterized by increased cytokine release. Because the role of fibroblasts in the bovine corpus luteum remains to be elucidated, the aim of this study was to elucidate the response of bovine luteal fibroblasts to inflammatory cytokines, tumor necrosis factor α (TNFα), and interleukin 1β (IL1β). Both cytokines induced canonical mitogen activated protein kinase (MAPK) signaling in luteal fibroblasts by phosphorylation of ERK1/2, p38 MAPK, and JNK. IL1β elevated expression and phosphorylation of cytosolic phospholipase A2 (cPLA<sub>2</sub>), an enzyme that mobilizes arachidonic acid for prostanoid synthesis. IL1β also elevated expression of prostaglandin-endoperoxide synthase 2 (PTGS2), another enzyme needed to synthesize prostanoids. IL1β increased PGF2α and PGE<sub>2</sub> levels in the culture medium over 20-fold. Inhibition of MAPKs with small-molecule inhibitors abrogated the stimulatory effects of IL1β. IL1β also induced prostaglandin production in steroidogenic cells; however, there was no elevation in cPLA<sub>2</sub>. Therefore, actions of IL1β differ based on ovarian cell type. All together, we have identified luteal fibroblasts as potential inflammatory mediators during luteal regression.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"596 ","pages":"Article 112420"},"PeriodicalIF":3.8,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sayantan Sur , Calum Stewart , Timothy A. Liddle , Ana Maria Monteiro , Irem Denizli , Gaurav Majumdar , Tyler J. Stevenson
{"title":"Molecular basis of photoinduced seasonal energy rheostasis in Japanese quail (Coturnix japonica)","authors":"Sayantan Sur , Calum Stewart , Timothy A. Liddle , Ana Maria Monteiro , Irem Denizli , Gaurav Majumdar , Tyler J. Stevenson","doi":"10.1016/j.mce.2024.112415","DOIUrl":"10.1016/j.mce.2024.112415","url":null,"abstract":"<div><div>Seasonal rhythms in photoperiod are a predictive cue used by many temperate-zone animals to time cycles of lipid accumulation. The neuroendocrine regulation of seasonal energy homeostasis and rheostasis are widely studied. However, the molecular pathways underlying tissue-specific adaptations remain poorly described. We conducted two experiments to examine long-term rheostatic changes in energy stability using the well-characterized photoperiodic response of the Japanese quail. In experiment 1, we exposed quails to photoperiodic transitions simulating the annual photic cycle and examined the morphology and fat deposition in liver, muscle, and adipose tissue. To identify changes in gene expression and molecular pathways during the vernal transition in lipid accumulation, we conducted transcriptomic analyses of adipose and liver tissues. Experiment 2 assessed whether the changes observed in Experiment 1 reflected constitutive levels or were due to time-of-day sampling. We identified increased expression of transcripts involved in adipocyte growth, such as <em>Cysteine Rich Angiogenic Inducer 61</em> and <em>Very Low-Density Lipoprotein Receptor</em>, and in obesity-linked disease resistance, such as <em>Insulin-Like Growth Factor Binding Protein 2</em> and <em>Apolipoprotein D</em>, in anticipation of body mass gain. Under long photoperiods, hepatic transcripts involved in fatty acid (FA) synthesis (<em>FA Synthase</em>, <em>FA Desaturase 2</em>) were down-regulated. Parallel upregulation of hepatic <em>FA Translocase</em> and <em>Pyruvate Dehydrogenase Kinase 4</em> expression suggests increased FA uptake and inhibition of the pyruvate dehydrogenase complex. Our findings demonstrate tissue-specific biochemical and molecular changes that drive photoperiod-induced adipogenesis. These findings can be used to determine conserved pathways that enable animals to accumulate fat without developing metabolic diseases.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112415"},"PeriodicalIF":3.8,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142676333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yiyun Xi , Ming Yang , Zebin Deng , Xiaofeng Xiong , Ling Wei , Juan Cai , Chengyuan Tang , Lin Sun
{"title":"ACSL5 promotes lipid deposition and lipoapoptosis in proximal tubular epithelial cells of diabetic kidney disease","authors":"Yiyun Xi , Ming Yang , Zebin Deng , Xiaofeng Xiong , Ling Wei , Juan Cai , Chengyuan Tang , Lin Sun","doi":"10.1016/j.mce.2024.112418","DOIUrl":"10.1016/j.mce.2024.112418","url":null,"abstract":"<div><h3>Background</h3><div>Lipoapoptosis in Proximal tubular epithelial cells (PTCs) are substantial in the etiology of diabetic kidney disease (DKD), yet the underlying mechanisms warrant further investigation. Acyl-CoA synthetase long-chain family member 5 (ACSL5) facilitates the formation of acyl-CoA, however, the precise role of ACSL5 in lipoapoptosis of PTCs in DKD remains inconclusive.</div></div><div><h3>Methods</h3><div>Transcriptomic data analysis identified the hub gene <em>Acsl5</em> associated with lipid metabolism in DKD. The expression of ACSL5 was examined in high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mice and high glucose/palmitic acid (HGPA)-induced mouse proximal tubular epithelial cell (BUMPT). Oil Red O staining, free fatty acids (FFA) ELISA assay, Western Blot, and morphological changes were employed to assess lipid deposition and lipoapoptosis. Furthermore, knockdown and overexpression of ACSL5 were conducted in BUMPT cells, followed by morphological assessment, Oil Red O staining, FFA ELISA assay and Western Blot analysis. Using the ChEA3 database, we predicted that STAT3 may transcriptionally regulate ACSL5. Subsequently, we knocked down STAT3 and evaluated <em>Acsl5</em> expression via RT-qPCR. Additionally, we investigated whether STAT3 modulates the impact of ACSL5 on lipoapoptosis through Western Blot analysis.</div></div><div><h3>Results</h3><div>We demonstrated, for the first time, a notable upregulation of ACSL5 expression in PTCs in HFD/STZ-induced diabetic mice, accompanied by increased the expression of FATP2, lipid accumulation and heightened lipoapoptosis. In HGPA-treated BUMPT cells, ACSL5 knockdown reduced the expression of FATP2, lipid deposition and lipoapoptosis, whereas its overexpression elevated the expression of FATP2 and exacerbated these effects. These findings strongly suggest that ACSL5 may exacerbate lipoapoptosis in PTCs within a diabetic milieu. From a molecular mechanism perspective, ACSL5 expression decreased after <em>Stat3</em> knockdown. Concurrent knockdown of <em>Stat3</em> and overexpression of <em>Acsl5</em> led to a mitigation of lipoapoptosis compared to sole <em>Acsl5</em> overexpression. Furthermore, STAT3 promotes the activation of <em>ACSL5</em> promoter under HGPA conditions.</div></div><div><h3>Conclusions</h3><div>In summary, our research identified ACSL5 as an important contributor exacerbating lipoapoptosis in the renal proximal tubules within diabetic environments. In addition, we found that ACSL5 is transcriptionally regulated by STAT3.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112418"},"PeriodicalIF":3.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Zhaoqing Xi , Ling Shu , Lingling Xiao , Xuesheng Fang , Mingyan Dai , Jing Wang , Yuan Wu , Junxia Zhang , Mingwei Bao
{"title":"Macrophage NLRP3 inflammasome mediates the effects of sympathetic nerve on cardiac remodeling in obese rats","authors":"Zhaoqing Xi , Ling Shu , Lingling Xiao , Xuesheng Fang , Mingyan Dai , Jing Wang , Yuan Wu , Junxia Zhang , Mingwei Bao","doi":"10.1016/j.mce.2024.112417","DOIUrl":"10.1016/j.mce.2024.112417","url":null,"abstract":"<div><div>Obesity-associated cardiac remodeling is characterized by cardiac sympathetic nerve over-activation and pro-inflammatory macrophage infiltration. We identified norepinephrine (NE), a sympathetic neurotransmitter, as a pro-inflammatory effector to activate macrophage NLRP3 inflammasome, which contributed to cardiac inflammation. In vivo, Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) for 12 weeks to establish obese rat models. Obese rats exhibited marked cardiac hypertrophy compared to normal rats. The expression of NLRP3 and interleukin (IL)-1β was upregulated, accompanied by CD68<sup>+</sup>NLRP3<sup>+</sup> macrophage infiltration in the hearts of the obese rats. The obese rats also showed increased sympathetic nerve activity. β-adrenergic receptor (AR) inhibition mitigated these changes. In vitro, sympathetic neurotransmitter NE significantly exacerbated palmitic acid (PA)-induced macrophage polarization toward pro-inflammatory type and NLRP3 inflammasome activation in THP-1 macrophages. It was further found that the pro-inflammatory role of NE is dependent on the activation of protein kinase A (PKA) and subsequently inhibition of β-arrestin2, which is an important regulator of the nuclear factor-kappa B (NF-κB) pathway.</div><div>This study identifies the neuro-immune axis as an important mediator in obesity-associated cardiac remodeling. Targeting the neuro-immune system may open therapeutic opportunities for the treatment of cardiac remodeling in obesity.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"596 ","pages":"Article 112417"},"PeriodicalIF":3.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668473","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Giovanni Levate , Yuan Wang , Riada McCredie , Megan Fenwick , Michael T. Rae , W. Colin Duncan , Katarzyna J. Siemienowicz
{"title":"Insights into the effects of sex and tissue location on the evolution of adipocyte dysfunction in an ovine model of polycystic ovary syndrome (PCOS)","authors":"Giovanni Levate , Yuan Wang , Riada McCredie , Megan Fenwick , Michael T. Rae , W. Colin Duncan , Katarzyna J. Siemienowicz","doi":"10.1016/j.mce.2024.112416","DOIUrl":"10.1016/j.mce.2024.112416","url":null,"abstract":"<div><div>Adipose tissue dysfunction is one of the features of Polycystic Ovary Syndrome (PCOS) with dysregulated adipogenesis, altered functional pathways and increased inflammation. It is increasingly clear that there are also male correlates of the hormonal and metabolic features of PCOS. We hypothesised that the effects of adipose tissue dysfunction are not sex-specific but rather fat depot-specific and independent of obesity. We used a clinically realistic ovine model of PCOS where pregnant sheep are injected with 100 mg of testosterone propionate twice weekly from day 62 to day 102 of gestation. We studied control and prenatally androgenised (PA) female and male offspring during adolescence and weight-matched control and PA female sheep during adulthood. We examined subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and in adult female sheep bone marrow adipose tissue (BMAT). Adipogenesis related gene expression in SAT was similar in adolescent female and male controls and the reduction in adipogenesis related gene expression by PA in female adipose tissue was not observed in males. Differences in expression of genes associated with adipose tissue function in adolescence in SAT driven by PA were found in both sexes. In adulthood, the changes seen in adolescent females were absent or reversed but there was an increase in inflammatory markers that was weight independent. In addition, BMAT showed increased inflammatory markers. Adipose dysfunction evolves with time and is focussed on SAT rather than VAT and is generally sex-specific although there are also effects of prenatal androgenisation on male SAT. In female adults, the inflammation seen in SAT is also present in BMAT and the development of blood cells in an inflammatory environment may have systemic implications.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112416"},"PeriodicalIF":3.8,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142668472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daniela Rosendo-Silva , Eduardo Lopes , Tamaeh Monteiro-Alfredo , Inês Falcão-Pires , Hans Eickhoff , Sofia Viana , Flávio Reis , Ana Salomé Pires , Ana Margarida Abrantes , Maria Filomena Botelho , Raquel Seiça , Paulo Matafome
{"title":"Corrigendum to “The adipose tissue melanocortin 3 receptor is targeted by ghrelin and leptin and may be a therapeutic target in obesity” [Mol. Cell. Endocrinol. 594 (2024), 112367]","authors":"Daniela Rosendo-Silva , Eduardo Lopes , Tamaeh Monteiro-Alfredo , Inês Falcão-Pires , Hans Eickhoff , Sofia Viana , Flávio Reis , Ana Salomé Pires , Ana Margarida Abrantes , Maria Filomena Botelho , Raquel Seiça , Paulo Matafome","doi":"10.1016/j.mce.2024.112410","DOIUrl":"10.1016/j.mce.2024.112410","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112410"},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Chen Liu , Limin Zhang , Siqi Li , Ruixi Zhou , Wenbo Wu , Yumei Liu , Ming Shu , Wanwei Li , Xiaohong Li
{"title":"Resveratrol attenuates Cr(VI)-induced disorders of glycolipid metabolism by regulating HNF1b/GPX1 in mice","authors":"Chen Liu , Limin Zhang , Siqi Li , Ruixi Zhou , Wenbo Wu , Yumei Liu , Ming Shu , Wanwei Li , Xiaohong Li","doi":"10.1016/j.mce.2024.112408","DOIUrl":"10.1016/j.mce.2024.112408","url":null,"abstract":"<div><div>Epidemiological studies have indicated that exposure to hexavalent chromium (Cr(VI)) is associated with increased morbidity in the population. Resveratrol (Res) is a polyphenolic compound known for its role in mitigating oxidative stress and inflammation. In this study, we investigated the effects of resveratrol on Cr(VI)-induced disorders of glycolipid metabolism and elucidated its mechanisms. Male C57BL/6 mice were exposed to resveratrol and Cr(VI) for 45 days. Cr(VI) exposure led to elevated blood glucose levels, impaired glucose tolerance and insulin resistance, oxidative and inflammatory responses, and alterations in glycolipid metabolism molecules such as PCK1 and SREBP1, along with inhibition of HNF1b and GPX1. Resveratrol pretreatment increased the expression of HNF1b and GPX1, reduced oxidative and inflammatory responses, and ultimately ameliorated Cr(VI)-induced glycolipid metabolism disorders. These findings suggest potential new targets for the prevention and treatment of dysglycolipidosis.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112408"},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Batoul Abi Zamer , Jasmin Shafarin , BasmaM. Sharaf , HamzaM. Al Hroub , Nelson C. Soares , Mohammad H. Semreen , Mawieh Hamad , Jibran Sualeh Muhammad
{"title":"Estrogen-mediated inhibition of purine metabolism and cell cycle arrest as a novel therapeutic approach in colorectal cancer","authors":"Batoul Abi Zamer , Jasmin Shafarin , BasmaM. Sharaf , HamzaM. Al Hroub , Nelson C. Soares , Mohammad H. Semreen , Mawieh Hamad , Jibran Sualeh Muhammad","doi":"10.1016/j.mce.2024.112414","DOIUrl":"10.1016/j.mce.2024.112414","url":null,"abstract":"<div><div>Purine metabolism is upregulated in various cancers including colorectal cancer (CRC). While previous work has elucidated the role of estrogen (E2) in metabolic reprogramming and ATP production, the effect of E2 on purine metabolism remains largely unknown. Herein, the impact of E2 signalling on purine metabolism in CRC cells was investigated using metabolome and transcriptome profiling of cell extracts derived from E2-treated HCT-116 cells with intact or silenced estrogen receptor alpha (ERα). Purine metabolic pathway enrichment analysis showed that 27 genes in the <em>de novo</em> purine synthesis pathway were downregulated in E2-treated CRC cells. Downstream consequences of E2 treatment including the induction of DNA damage, cell cycle arrest, and apoptosis were all shown to be ERα-dependent. These findings demonstrate, for the first time, that E2 exerts a significant anti-growth and survival effect in CRC cells by targeting the purine synthesis pathway in a ERα-dependent manner, meriting further investigation of the therapeutic utility of E2 signalling in CRC.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"596 ","pages":"Article 112414"},"PeriodicalIF":3.8,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}