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Full-Text Articles in Medical Physiology
Epigenetic Mechanisms Differentially Regulate Blood Pressure And Renal Dysfunction In Male And Female Npr1 Haplotype Mice, Prerna Kumar, Kandasamy Neelamegam, Chandramohan Ramasamy, Ramachandran Samivel, Huijing Xia, Daniel R. Kapusta, Kailash N. Pandey
Epigenetic Mechanisms Differentially Regulate Blood Pressure And Renal Dysfunction In Male And Female Npr1 Haplotype Mice, Prerna Kumar, Kandasamy Neelamegam, Chandramohan Ramasamy, Ramachandran Samivel, Huijing Xia, Daniel R. Kapusta, Kailash N. Pandey
School of Graduate Studies Faculty Publications
We determined the epigenetic mechanisms regulating mean arterial pressure (MAP) and renal dysfunction in guanylyl cyclase/natriuretic peptide receptor-A (GC-A/NPRA) gene-targeted mice. The Npr1 (encoding NPRA) gene-targeted mice were treated with class 1 specific histone deacetylase inhibitor (HDACi) mocetinostat (MGCD) to determine the epigenetic changes in a sex-specific manner. Adult male and female Npr1 haplotype (1-copy; Npr1+/−), wild-type (2-copy; Npr1+/+), and gene-duplicated heterozygous (3-copy; Npr1++/+) mice were intraperitoneally injected with MGCD (2 mg/kg) for 14 days. BP, renal function, histopathology, and epigenetic changes were measured. One-copy male mice showed significantly increased MAP, renal dysfunction, and fibrosis than 2-copy and 3-copy mice. …
Lysine Methyltransferase Nsd1 And Cancers: Any Role In Melanoma?, Imène Krossa, Thomas Strub, Andrew E Aplin, Robert Ballotti, Corine Bertolotto
Lysine Methyltransferase Nsd1 And Cancers: Any Role In Melanoma?, Imène Krossa, Thomas Strub, Andrew E Aplin, Robert Ballotti, Corine Bertolotto
Department of Cancer Biology Faculty Papers
Epigenetic regulations, that comprise histone modifications and DNA methylation, are essential to processes as diverse as development and cancer. Among the histone post-translational modifications, lysine methylation represents one of the most important dynamic marks. Here, we focused on methyltransferases of the nuclear binding SET domain 1 (NSD) family, that catalyze the mono- and di-methylation of histone H3 lysine 36. We review the loss of function mutations of NSD1 in humans that are the main cause of SOTOS syndrome, a disease associated with an increased risk of developing cancer. We then report the role of NSD1 in triggering tumor suppressive or …
Developmental Origins Of Health And Disease: Current Knowledge And Potential Mechanisms, Daniel J. Hoffman, Rebecca M. Reynolds, Daniel B. Hardy
Developmental Origins Of Health And Disease: Current Knowledge And Potential Mechanisms, Daniel J. Hoffman, Rebecca M. Reynolds, Daniel B. Hardy
Physiology and Pharmacology Publications
Epidemiologic and clinical research has provided a large body of evidence supporting the developmental origins of health and disease (DOHaD), but there has been a relative dearth of mechanistic studies in humans due to the complexity of working with large, longitudinal cohorts. Nonetheless, animal models of undernutrition have provided substantial evidence for the potential epigenetic, metabolic, and endocrine mechanisms behind DOHaD. Furthermore, recent research has explored the interaction between the environment and the gastrointestinal system by investigating how the gut microbial ecology may impact the capacity for nutrient processing and absorption in a manner that may limit growth. This review …
Increased Incidence Of Non-Alcoholic Fatty Liver Disease In Male Rat Offspring Exposed To Fluoxetine During Fetal And Neonatal Life Involves The Nlrp3 Inflammasome And Augmented De Novo Hepatic Lipogenesis., Nicole E De Long, Daniel B Hardy, Noelle Ma, Alison C Holloway
Increased Incidence Of Non-Alcoholic Fatty Liver Disease In Male Rat Offspring Exposed To Fluoxetine During Fetal And Neonatal Life Involves The Nlrp3 Inflammasome And Augmented De Novo Hepatic Lipogenesis., Nicole E De Long, Daniel B Hardy, Noelle Ma, Alison C Holloway
Physiology and Pharmacology Publications
Up to 10% of women take selective serotonin reuptake inhibitors (SSRI) during pregnancy. Children exposed to SSRIs in utero have an increased risk of being overweight suggesting that fetal exposure to SSRIs can cause permanent metabolic changes. We have previously shown in rats that fetal and neonatal exposure to the SSRI antidepressant fluoxetine results in metabolic perturbations including increased hepatic triglyceride content; a hallmark of non-alcoholic fatty liver disease (NAFLD). Therefore, the aim of this study was to identify the mechanism(s) underlying the fluoxetine-induced increase in intrahepatic triglyceride content. Female nulliparous Wistar rats were given vehicle or fluoxetine (10 mg/kg/day) …
Maternal Undernutrition And Long-Term Effects On Hepatic Function, Daniel B. Hardy
Maternal Undernutrition And Long-Term Effects On Hepatic Function, Daniel B. Hardy
Physiology and Pharmacology Publications
Undernutrition in utero, regardless of the source, can impair proper liver development leading to long-term metabolic dysfunction. Understanding the molecular mechanisms underlying how nutritional deficits during perinatal life lead to permanent alterations in hepatic gene expression will provide better therapeutic strategies to alleviate the undernourished liver in postnatal life. This chapter addresses the different experimental models of undernutrition in utero, and highlights the direct and indirect mechanisms involved leading to metabolic diseases in the liver. These include hypoxia, oxidative stress, epigenetic alterations, and endoplasmic reticulum (ER) stress. In addition, promising perinatal nutritional and pharmaceutical interventions are highlighted which …
Perinatal Malnutrition And Epigenetic Regulation Of Long-Term Metabolism In The Liver And Adipose Tissue, Daniel B. Hardy
Perinatal Malnutrition And Epigenetic Regulation Of Long-Term Metabolism In The Liver And Adipose Tissue, Daniel B. Hardy
Physiology and Pharmacology Publications
Maternal malnutrition in perinatal life can have long-lasting adverse effects on glucose and lipid homeostasis in the offspring, culminating in dyslipidemia, insulin resistance and obesity. Understanding the molecular mechanisms underlying how these nutritional deficits during perinatal life lead to permanent changes in hepatic and adipose function will provide efficacious therapeutic strategies to mitigate these metabolic defects short- and long-term. This chapter addresses how epigenetic mechanisms mediate alterations in hepatic and adipose gene expression identified from clinical studies and different experimental models of maternal malnutrition. These include DNA methylation, post-translational histone modifications, and microRNAs.
Ovarian Tumour Growth Is Characterized By Mevalonate Pathway Gene Signature In An Orthotopic, Syngeneic Model Of Epithelial Ovarian Cancer., James B Greenaway, Carl Virtanen, Kata Osz, Tamas Revay, Daniel Hardy, Trevor Shepherd, Gabriel Dimattia, Jim Petrik
Ovarian Tumour Growth Is Characterized By Mevalonate Pathway Gene Signature In An Orthotopic, Syngeneic Model Of Epithelial Ovarian Cancer., James B Greenaway, Carl Virtanen, Kata Osz, Tamas Revay, Daniel Hardy, Trevor Shepherd, Gabriel Dimattia, Jim Petrik
Physiology and Pharmacology Publications
Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer and often is not detected until late stages when cancer cells transcoelomically metastasize to the abdomen and typically become resistant to therapy resulting in very low survival rates. We utilize an orthotopic, syngeneic mouse model to study late stage disease and have discovered that the tumor cells within the abdominal ascites are irreversibly re-programmed, with an increased tumorigenicity and resistance to apoptosis. The goal of this study was to characterize the reprogramming that occurred in the aggressive ascites-derived cells (28-2 cells) compared to the original cell line used for tumor …