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glucose regulated protein 94 and heart

A Burgeiro, A C Fonseca, D Espinoza, L Carvalho, N Lourenço, M Antunes, E Carvalho
BACKGROUND: Cardiovascular diseases (CVDs) are leading cause of death and primary cause of morbidity and mortality in diabetic population. Epicardial adipose tissue (EAT) covers the heart's surface and is a source of biomolecules regulating heart and blood vessel physiology. The protective activation of the unfolded protein response (UPR) and autophagy allows the cardiomyocyte reticular network to restore energy and/or nutrient homeostasis and to avoid cell death. However, an excessive or prolonged UPR activation can trigger cell death...
April 3, 2018: Biochimica et Biophysica Acta
Jian-Lin Ma, Wen-Ling Guo, Xue-Mei Chen
MicroRNA (miR)-150 has been demonstrated to protect the heart from ischemic injury. However, the protective effect of miR‑150 in hypoxia‑injured cardiomyocytes remains unclear. The present study aimed to investigate the target gene of miR‑150 and the underlying molecular mechanisms of miR‑150 in hypoxia‑induced cardiomyocyte apoptosis. Using the hypoxia model of human cardiomyocytes (HCMs) in vitro, it was demonstrated that miR‑150 was markedly inhibited in HCMs after hypoxia treatment. Overexpressing miR‑150 significantly decreased hypoxia‑induced HCM death and apoptosis...
March 2018: Molecular Medicine Reports
Ana P Pinto, Alisson L da Rocha, Luciana da C Oliveira, Gustavo P Morais, Larissa G de Vicente, Dennys E Cintra, José R Pauli, Leandro P Moura, Eduardo R Ropelle, Adelino S R da Silva
Recently, we demonstrated that different running overtraining (OT) protocols with the same external load, but performed downhill (OTR/down), uphill (OTR/up), and without inclination (OTR), led to hepatic fat accumulation. As the disruption of endoplasmic reticulum (ER) homeostasis is linked to animal models of fatty liver disease, we investigated the effects of these OT models on the proteins related to ER stress (i.e., BiP, inositol-requiring enzyme 1, protein kinase RNA-like endoplasmic reticulum kinase, eIF2alpha, ATF6beta, and glucose-regulated protein 94) and apoptosis (C/EBP-homologous protein, Caspase-3, 4, and 12, Bax, and tumor necrosis factor receptor-associated factor 2) in livers of C57BL/6 mice...
2017: Frontiers in Endocrinology
Guochen Wang, Hongping Huang, Huan Zheng, Yonggui He, Yidong Zhang, Zhelong Xu, Liu Zhang, Jinkun Xi
The purpose of this study was to determine whether Zn(2+) is involved in endoplasmic reticulum (ER) stress inhibition-induced cardioprotection against ischemia/reperfusion (I/R) injury by modulation of the mitochondrial permeability transition pore (mPTP) opening. Isolated rat hearts were subjected to 30-min regional ischemia followed by 2 h of reperfusion. Expression of glucose regulated protein 78 (GRP 78 or BIP), an ER homeostasis marker, was not increased during ischemia but was increased upon reperfusion, indicating that ER stress was initiated upon reperfusion but not during ischemia...
November 2016: Biological Trace Element Research
Matthew Fenech, Jelena Gavrilovic, Paul Malcolm, Andoni Toms, Jeremy Turner
BACKGROUND: Metabolically unhealthy obesity is associated with insulin resistance. Dysfunctional adipose tissue remodelling might explain features of this disorder, such as chronic white adipose tissue inflammation, adipocyte hypertrophy, and ectopic lipid deposition. Metalloproteinases and their tissue inhibitors (TIMPs) have been implicated in human adipose tissue remodelling. In a cross-sectional study, we investigated the association of adipose metalloproteinase and TIMP expression with whole-body lipid distribution and insulin resistance...
February 26, 2015: Lancet
Yu Liu, Jie Wang, Shu-Ying Qi, Lei-Sheng Ru, Chao Ding, Hai-Jun Wang, Jing-Shan Zhao, Jing-Jing Li, Ai-Ying Li, Dong-Mei Wang
BACKGROUND: Endoplasmic reticulum (ER) stress plays an important role in mediating ischemic heart cell death. The aim of this study was to investigate whether manipulation of a key factor of the ER stress pathway, eukaryotic translation initiation factor 2 subunit α (eIF2α), can change the natural history of heart failure (HF). METHODS: HF was induced using coronary artery ligation in adult rats and a selective eIF2α dephosphorylation inhibitor, salubrinal (Sal), was used...
March 2014: Canadian Journal of Cardiology
Clifford Dl Folmes, Grzegorz Sawicki, Virgilio Jj Cadete, Grant Masson, Amy J Barr, Gary D Lopaschuk
BACKGROUND: During and following myocardial ischemia, glucose oxidation rates are low and fatty acids dominate as a source of oxidative metabolism. This metabolic phenotype is associated with contractile dysfunction during reperfusion. To determine the mechanism of this reliance on fatty acid oxidation as a source of ATP generation, a functional proteomics approach was utilized. RESULTS: 2-D gel electrophoresis of mitochondria from working rat hearts subjected to 25 minutes of global no flow ischemia followed by 40 minutes of aerobic reperfusion identified 32 changes in protein abundance compared to aerobic controls...
July 9, 2010: Proteome Science
Alexandra R Cook, Sonya C Bardswell, Subashini Pretheshan, Kushal Dighe, Gajen S Kanaganayagam, Rita I Jabr, Sabine Merkle, Michael S Marber, Stefan Engelhardt, Metin Avkiran
Sarcolemmal Na(+)/H(+) exchanger (NHE) activity, which is provided by the NHE isoform 1 (NHE1), has been implicated in ischemia/reperfusion-induced myocardial injury in animal models and humans, on the basis of studies with pharmacological NHE1 inhibitors. We generated a transgenic (TG) mouse model with cardiac-specific over-expression of NHE1 to determine whether this would be sufficient to increase myocardial susceptibility to ischemia/reperfusion-induced injury. TG mouse hearts exhibited increased sarcolemmal NHE activity and normal morphology and function...
February 2009: Journal of Molecular and Cellular Cardiology
Marina Marini, Rosa Lapalombella, Vittoria Margonato, Raffaella Ronchi, Michele Samaja, Cristina Scapin, Luisa Gorza, Tullia Maraldi, Paolo Carinci, Carlo Ventura, Arsenio Veicsteinas
To improve current knowledge of the molecular mechanisms underlying exercise-induced cardioprotection in a rat model of mild exercise training, Sprague-Dawley rats were trained to run on a treadmill up to 55% of their maximal oxygen uptake for 1 h/day, 3 days/week, 14 weeks, with age-matched sedentary controls (n = 20/group). Rats were sacrificed 48 h after the last training session. Despite lack of cardiac hypertrophy, training decreased blood hemoglobin (7.94 +/- 0.21 mM vs. 8.78 +/- 0.23 mM, mean +/- SE, P = 0...
March 2007: European Journal of Applied Physiology
Hong Li, Ying-Bin Xiao, Yu-Qi Gao, Tian-De Yang
Mitochondrial ATP sensitive potassium channels (mitoK(ATP) channels) are involved in the cardioprotection afforded by ischemic preconditioning (IPC) and diazoxide, a selective mitoK(ATP) channel opener. The activation of some kinases, including phoshoprotein kinase (PKC)-epsilon and mitogen-activating protein kinases (MAPK), is involved in signal conduction of preconditioning downstream from mitoK(ATP) channel opening. Diazoxide can open mitoK(ATP) channels and activate PKC-epsilon, which will phosphorylate some substrate proteins...
2006: Drug Metabolism and Drug Interactions
Joshua J Martindale, Rayne Fernandez, Donna Thuerauf, Ross Whittaker, Natalie Gude, Mark A Sussman, Christopher C Glembotski
Ischemia/reperfusion (I/R) affects the integrity of the endoplasmic reticulum (ER), the site of synthesis and folding of numerous proteins. Therefore, I/R may activate the unfolded protein response (UPR), resulting in the induction of a collection of ER stress proteins, many of which are protective and function to resolve the ER stress. In this study, we showed that when mouse hearts were subjected to ex vivo I/R, the levels of 2 ER stress-inducible markers of the UPR, the ER-targeted cytoprotective chaperones glucose-regulated proteins 78 and 94 (GRP78 and GRP94), were increased, consistent with I/R-mediated UPR activation in the heart...
May 12, 2006: Circulation Research
E Szabados, G M Fischer, K Toth, B Csete, B Nemeti, K Trombitas, T Habon, D Endrei, B Sumegi
The short term cardiac side-effects of AZT (3'-azido-3'-deoxythymidine, zidovudine) was studied in rats to understand the biochemical events contributing to the development of AZT-induced cardiomyopathy. Developing rats were treated with AZT (50 mg/kg/day) for 2 wk and the structural and functional changes were monitored in the cardiac muscle. AZT treatment provoked a surprisingly fast appearance of cardiac malfunctions in developing animals characterized by prolonged RR, PR and QT intervals and J point depression...
February 1999: Free Radical Biology & Medicine
M Vitadello, P Colpo, L Gorza
The glucose-regulated protein GRP94 is a stress-inducible glycoprotein that is known to be constitutively and ubiquitously expressed in the endoplasmic reticulum of mammalian cells. From a rabbit heart cDNA library we isolated four overlapping clones coding for the rabbit homologue of GRP94 mRNA. Northern blot analysis shows that a 3200 nt mRNA species corresponding to GRP94 mRNA is detectable in several tissues and it is 5-fold more abundant in the heart than in the skeletal muscle. Hybridization analysis in situ shows that GRP94 mRNA accumulates in cardiac myocytes, whereas in skeletal muscles it is not detectable in myofibres...
June 1, 1998: Biochemical Journal
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