Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 44, Issue 6, Pages 972-979Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2012.03.004
Keywords
Activating transcription factor 6 alpha; Glucose regulated protein 78; Chronic hypoxia; Myocardial adaptation; Re-oxygenation injury
Categories
Funding
- National Natural Science Foundation of China (NSFC) [30972957, 81000077]
Ask authors/readers for more resources
Hypoxic states are generally associated with cardiovascular disease. Adaptation to chronic hypoxia is one well-defined means of improving cardiac tolerance to certain kinds of stresses. However, the details of the mechanisms underlying myocardial adaptation to chronic hypoxia are still poorly understood. Hypoxia stresses the endoplasmic reticulum and activates unfolded protein response. However, the behavior of individual signaling pathways can vary markedly over time. By examining myocardial samples from patients with cyanotic congenital cardiac defects, we detected endoplasmic reticulum stress and found that, out of all the components of the unfolded protein response, only activating transcription factor 6 alpha limb was activated in cyanotic patients. The activation of activating transcription factor 6 alpha and expression of glucose regulated protein 78 were notably induced in cardiac myocytes cultured for prolonged hypoxia (1% O-2 for 48 h). When the activation of activating transcription factor 6 alpha under prolonged hypoxia was blocked by chemical inhibitor Brefeldin A, the rate of apoptosis among cardiac myocytes increased and levels of cleaved caspase 3 and cleaved poly ADP ribose polymerase also increased significantly. After the expression of activating transcription factor 6 alpha was knocked down, the activity of cardiac myocytes under prolonged hypoxia decreased and the phosphorylation of c-Jun NH2-terminal kinases increased during the re-oxygenation process (after 72 h of hypoxia). Together, these results indicate that activating transcription factor 6 alpha plays a pivotal role in myocardial adaptation to chronic hypoxia and that the activation of activating transcription factor 6 alpha is one possible mechanism of myocardial preconditioning. (C) 2012 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available