scholarly journals Sex modifies exercise and cardiac adaptation in mice

2004 ◽  
Vol 287 (6) ◽  
pp. H2768-H2776 ◽  
Author(s):  
John P. Konhilas ◽  
Alexander H. Maass ◽  
Stephen W. Luckey ◽  
Brian L. Stauffer ◽  
Eric N. Olson ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cardiac Myocyte ◽  
Glycogen Synthase ◽  
Mitogen Activated Protein Kinase ◽  
Dominant Factor ◽  
Mouse Strains ◽  
Hypertrophic Response ◽  
Cardiac Adaptation ◽  
Mitogen Activated Protein ◽  
Gsk 3Β

How an individual's sex and genetic background modify cardiac adaptation to increased workload is a topic of great interest. We systematically evaluated morphological and physiological cardiac adaptation in response to voluntary and forced exercise. We found that sex/gender is a dominant factor in exercise performance (in two exercise paradigms and two mouse strains) and that females of one of these strains have greater capacity to increase their cardiac mass in response to similar amounts of exercise. To explore the biochemical mechanisms for these differences, we examined signaling pathways previously implicated in cardiac hypertrophy. Ca2+/calmodulin-dependent protein kinase (CaMK) activity was significantly greater in males compared with females and increased after voluntary cage-wheel exposure in both sexes, but the proportional increase in CaMK activity was twofold higher in females compared with males. Phosphorylation of glycogen synthase kinase-3β (GSK-3β) was evident after 7 days of cage-wheel exposure in both sexes and remained elevated in females only by 21 days of exercise. Despite moderate increases in myocyte enhancer factor-2 (a downstream effector of CaMK) transcriptional activity and phosphorylation of Akt with exercise, there were no sex differences. Mitogen-activated protein kinase signaling components (p38 mitogen-activated protein kinase and extracellular regulated kinase 1/2) were not different between male and female mice and were not affected by exercise. We conclude that females have increased exercise capacity and increased hypertrophic response to exercise. We have also identified sex-specific differences in hypertrophic signaling within the cardiac myocyte that may contribute to sexual dimorphism in exercise and cardiac adaptation to exercise.

The role of the inhibition of glutathione-S-transferase in the protective mechanisms of ischemic postconditioning

2013 ◽  
Vol 91 (8) ◽  
pp. 625-632 ◽  
Author(s):  
Borbála Balatonyi ◽  
Balázs Gasz ◽  
Viktória Kovács ◽  
János Lantos ◽  
Gábor Jancsó ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Annexin V ◽  
Mitogen Activated Protein Kinase ◽  
Neonatal Rat ◽  
Control Group ◽  
Glutathione S Transferase ◽  
Protective Mechanisms ◽  
Flow Cytometric ◽  
Mitogen Activated Protein ◽  
Gsk 3Β

The antioxidant glutathione-S-transferase (GST) is a crucial determinant of the development of ischaemic−reperfusion (I/R) injury, and plays a pivotal role in the regulation of the mitogen activated protein kinase (MAPK) pathways involved in stress response and apoptosis. The aim of this study was to investigate whether inhibition of GST can abolish the benefit of ischaemic postconditioning (IPoC). A neonatal rat cardiomyocyte cell culture was prepared and divided into 6 groups: (I) control group without treatment; (II) cells exposed to simulated I/R; (III) simulated I/R (sI/R) with IPoC; (IV) ethacrynic acid (EA) alone; (V) sI/R with EA; and (VI) sI/R and IPoC together with EA. Viability of the cells was measured by MTT assay, the quantity of apoptotic cells was assessed by flow cytometry following annexin V-FITC − propidium-iodide double staining. The activation of JNK, p38, ERK/p42-p44 MAPKs, and GSK-3β protein kinase was determined by flow-cytometric assay. GST inhibition markedly increased the apoptosis and decreased the cell viability despite IPoC. The protective effect of IPoC was lost in GST-inhibited groups for all MAPKs and GSK-3β. GST activity is required for the survival of cultured cardiomyocytes under stress conditions. GST inhibition was associated with differential activation of MAP and the protein kinases regulating these pathways in the process of ischaemic postconditioning.

scholarly journals The activation of protein kinase B by H2O2 or heat shock is mediated by phosphoinositide 3-kinase and not by mitogen-activated protein kinase-activated protein kinase-2

1998 ◽  
Vol 336 (1) ◽  
pp. 241-246 ◽  
Author(s):  
Morag SHAW ◽  
Philip COHEN ◽  
Dario R. ALESSI
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Protein Kinase ◽  
Glycogen Synthase ◽  
Protein Kinase B ◽  
Osmotic Shock ◽  
Mitogen Activated Protein Kinase ◽  
Protein Synthesis Inhibitor ◽  
Mitogen Activated Protein ◽  
Sb 203580

Protein kinase B (PKB) isoforms became activated [and glycogen synthase kinase-3 (GSK3) became inhibited] when mouse Swiss 3T3 fibroblasts were exposed to oxidative stress (H2O2) or heat shock, but not when they were exposed to osmotic shock (0.5 M sorbitol or 0.7 M NaCl), chemical stress (sodium arsenite), the protein-synthesis inhibitor anisomycin, or UV radiation. In contrast, all seven stimuli activated mitogen-activated protein kinase-activated protein kinase-2 (MAPKAP-K2). The activation of MAPKAP-K2 was suppressed by the drug SB 203580, but not by inhibitors of phosphoinositide (phosphatidylinositide, PI) 3-kinase. In contrast, the activation of PKB isoforms and the inhibition of GSK3 by oxidative stress or heat shock were prevented by inhibitors of PI 3-kinase, but not by SB 203580. Thus the activation of PKB by oxidative stress or heat shock is mediated by PI 3-kinase and not by MAPKAP-K2. PKBα and PKBγ were also activated by heat shock and oxidative stress in human embryonic kidney 293 cells and PKBγ was activated by heat shock in NIH 3T3 cells; in each case activation was suppressed by inhibitors of PI 3-kinase. The activation of PKB isoforms by H2O2 may underlie some of the insulin-mimetic effects of this compound.

scholarly journals Pioglitazone Protected against Cardiac Hypertrophy via Inhibiting AKT/GSK3βand MAPK Signaling Pathways

PPAR Research ◽  
2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Wen-Ying Wei ◽  
Zhen-Guo Ma ◽  
Si-Chi Xu ◽  
Ning Zhang ◽  
Qi-Zhu Tang
Keyword(s):  
Protein Kinase ◽  
Cardiac Hypertrophy ◽  
Glycogen Synthase ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Neonatal Rat ◽  
Aortic Banding ◽  
Hypertrophic Response

Peroxisome proliferator activated receptorγ(PPARγ) has been closely involved in the process of cardiovascular diseases. This study was to investigate whether pioglitazone (PIO), a PPARγagonist, could protect against pressure overload-induced cardiac hypertrophy. Mice were orally given PIO (2.5 mg/kg) from 1 week after aortic banding and continuing for 7 weeks. The morphological examination and biochemical analysis were used to evaluate the effects of PIO. Neonatal rat ventricular cardiomyocytes were also used to verify the protection of PIO against hypertrophy in vitro. The results in our study demonstrated that PIO remarkably inhibited hypertrophic response induced by aortic banding in vivo. Besides, PIO also suppressed cardiac fibrosis in vivo. PIO treatment also inhibited the activation of protein kinase B (AKT)/glycogen synthase kinase-3β(GSK3β) and mitogen-activated protein kinase (MAPK) in the heart. In addition, PIO alleviated angiotensin II-induced hypertrophic response in vitro. In conclusion, PIO could inhibit cardiac hypertrophy via attenuation of AKT/GSK3βand MAPK pathways.

scholarly journals Role of 14-3-3-Mediated p38 Mitogen-Activated Protein Kinase Inhibition in Cardiac Myocyte Survival

2003 ◽  
Vol 93 (11) ◽  
pp. 1026-1028 ◽  
Author(s):  
Shaosong Zhang ◽  
Jie Ren ◽  
Cindy E. Zhang ◽  
Ilya Treskov ◽  
Yibin Wang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cardiac Myocyte ◽  
Mitogen Activated Protein Kinase ◽  
Kinase Inhibition ◽  
Protein Kinase Inhibition ◽  
Mitogen Activated Protein

Myeloid-Derived Growth Factor Promotes Intestinal Glucagon-Like Peptide-1 Production in Male Mice With Type 2 Diabetes

Endocrinology ◽  
2020 ◽  
Vol 161 (2) ◽  
Author(s):  
Li Wang ◽  
Yixiang Li ◽  
Bei Guo ◽  
Jiajia Zhang ◽  
Biao Zhu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factor ◽  
Protein Kinase ◽  
Cardiac Myocyte ◽  
Glycogen Synthase ◽  
Mitogen Activated Protein Kinase ◽  
Positive Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Myeloid-derived growth factor (MYDGF), which is produced by bone marrow–derived cells, mediates cardiac repair following myocardial infarction by inhibiting cardiac myocyte apoptosis to subsequently reduce the infarct size. However, the function of MYDGF in the incretin system of diabetes is still unknown. Here, loss-of-function and gain-of-function experiments in mice revealed that MYDGF maintains glucose homeostasis by inducing glucagon-like peptide-1 (GLP-1) production and secretion and that it improves glucose tolerance and lipid metabolism. Treatment with recombinant MYDGF increased the secretion and production of GLP-1 in STC-1 cells in vitro. Mechanistically, the positive effects of MYDGF are potentially attributable to the activation of protein kinase A/glycogen synthase kinase 3β/β-catenin (PKA/GSK-3β/β-catenin) and mitogen-activated protein kinase (MAPK) kinases/extracellular regulated protein kinase (MEK/ERK) pathways. Based on these findings, MYDGF promotes the secretion and production of GLP-1 in intestinal L-cells and potentially represents a potential therapeutic medication target for type 2 diabetes.

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