Characterization and Mechanism of Stress-induced Translocation of 78-Kilodalton Glucose-regulated Protein (GRP78) to the Cell Surface

Journal of Biological Chemistry, Journal Year: 2015, Volume and Issue: 290(13), P. 8049 - 8064

Published: Feb. 12, 2015

Language: Английский

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Endoplasmic Reticulum Chaperone GRP78 Protects Heart From Ischemia/Reperfusion Injury Through Akt Activation

Circulation Research, Journal Year: 2018, Volume and Issue: 122(11), P. 1545 - 1554

Published: April 18, 2018

Rationale: Restoration of coronary artery blood flow is the most effective means ameliorating myocardial damage triggered by ischemic heart disease. However, reperfusion elicits an increment additional injury to myocardium. Accumulating evidence indicates that unfolded protein response (UPR) in cardiomyocytes activated ischemia/reperfusion (I/R) injury. Xbp1s (spliced X-box binding 1), highly conserved branch response, protective cardiac I/R GRP78 (78 kDa glucose-regulated protein), a master regulator UPR and target, upregulated after I/R. its role during remains largely undefined. Objective: To elucidate cardiomyocyte using both vitro vivo approaches. Methods Results: Simulated cultured neonatal rat ventricular myocytes induced apoptotic cell death strong activation GRP78. Overexpression significantly protected from I/R-induced death. Furthermore, cardiomyocyte-specific overexpression ameliorated vivo. Exploration underlying mechanisms revealed mitigates cellular suppressing accumulation reactive oxygen species. We go on show GRP78-mediated cytoprotective involves plasma membrane translocation interaction with PI3 kinase, culminating stimulation Akt. This required as inhibition Akt pathway blunted antioxidant activity cardioprotective effects Conclusions: induction stimulates signaling protects against oxidative stress, which together protect cells damage.

Language: Английский

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Adapting to stress — chaperome networks in cancer

Nature reviews. Cancer, Journal Year: 2018, Volume and Issue: 18(9), P. 562 - 575

Published: May 23, 2018

Language: Английский

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Dual role of Endoplasmic Reticulum Stress-Mediated Unfolded Protein Response Signaling Pathway in Carcinogenesis

International Journal of Molecular Sciences, Journal Year: 2019, Volume and Issue: 20(18), P. 4354 - 4354

Published: Sept. 5, 2019

Cancer constitutes a grave problem nowadays in view of the fact that it has become one main causes death worldwide. Poor clinical prognosis is presumably due to cancer cells metabolism as tumor microenvironment affected by oxidative stress. This event triggers adequate cellular response and thereby creates appropriate conditions for further progression. Endoplasmic reticulum (ER) stress occurs when balance between an ability ER fold transfer proteins degradation misfolded ones distorted. Since organelle relatively sensitive damage, aforementioned swiftly cause activation unfolded protein (UPR) signaling pathway. The output UPR, depending on numerous factors, may vary switch pro-survival pro-apoptotic branch, hence displays opposing effects deciding fate cell. role UPR-related tumorigenesis, such binding immunoglobulin (BiP) inositol-requiring enzyme-1α (IRE1α), activating transcription factor 6 (ATF6) or kinase R (PKR)-like endoplasmic (PERK), already been specifically described so far. Nevertheless, paradoxical outcomes UPR well gaps current knowledge, still needs be investigated. Herein we would like elicit actual link neoplastic diseases pathway, considering its major branches discussing potential use development novel, anti-cancer, targeted therapy.

Language: Английский

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Grp78 Loss in Epithelial Progenitors Reveals an Age-linked Role for Endoplasmic Reticulum Stress in Pulmonary Fibrosis

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2019, Volume and Issue: 201(2), P. 198 - 211

Published: Nov. 18, 2019

Alveolar epithelial cell (AEC) injury and dysregulated repair are implicated in the pathogenesis of pulmonary fibrosis. Endoplasmic reticulum (ER) stress AEC has been observed idiopathic fibrosis (IPF), a disease aging.

Language: Английский

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