Document Detail

Prevention of export of anoxia/reoxygenation injury from ischemic to non-ischemic cardiomyocytes via inhibition of endocytosis.
MedLine Citation:
PMID:  24778168     Owner:  NLM     Status:  Publisher    
Myocardial infarct size is determined by death of non-ischemic border zone cardiomyocytes caused by export of injury signals from the infarct zone. The countermeasures to limit infarct size, therefore, should be aimed at non-selective blocking of most, if not all, injury signals from entering non-ischemic cells. To test whether inhibition of endocytosis might limit infarct size, HL-1 cardiomyocytes were subjected to anoxia (6 hrs) and reoxygenation (1 hr). Anoxic and reoxygenated cells showed multifold increase in mitochondrial reactive oxygen species (ROS) production accompanied with upregulation of scavenger receptors LOX-1 and CD36 and stimulation of stress signals, including NADPH oxidase subunit P22(phox), SOD2 and Beclin-1. Incubation of healthy cardiomyocytes in the media from anoxic and reoxygenated cells (conditioned media) resulted in qualitatively similar responses, including increase in generation of mitochondrial ROS, P22(phox), SOD2 and Beclin-1. Anoxia and reoxygenation caused collapse of clathrin-mediated endocytosis and stimulation of macropinocytosis whereas in the cultures exposed to conditioned media activity of endocytosis was uniformly higher. Conditioned media also significantly aggravated cytotoxic effects of TNFα and angiotensin II, and suppression of endocytosis reversed these trends resulting in overall increase of metabolic activity. Moreover, inhibition of endocytosis prevented binding of oxidized cellular fragments with greater efficiency than targeted neutralization of scavenger receptor LOX-1. Many of the observations in HL-1 cardiomyocytes were confirmed in primary cardiomyocyte cultures. Our data suggest that endocytosis is upregulated in the border zone cardiomyocytes, and inhibition of endocytosis may be an effective approach to prevent export of injury signals from the infarct zone.
Magomed Khaidakov; Federico Mercanti; Xianwei Wang; Zufeng Ding; Yao Dai; Francesco Romeo; Tatsuya Sawamura; Jawahar L Mehta
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-4-28
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  Am. J. Physiol. Heart Circ. Physiol.     Publication Date:  2014 Apr 
Date Detail:
Created Date:  2014-4-29     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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