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Nitric oxide-induced cell death in the heart: the role of autophagy.
- Source :
-
Autophagy [Autophagy] 2007 Jul-Aug; Vol. 3 (4), pp. 347-9. Date of Electronic Publication: 2007 Jul 23. - Publication Year :
- 2007
-
Abstract
- There is unequivocal evidence of autophagy in the heart, both in human hearts from patients who experienced heart failure and in experimental models of myocardial ischemia and reperfusion. Whether autophagy is involved in the pathophysiology of these conditions is controversial as studies suggest inhibition of Beclin 1 can increase or decrease cardiomyocyte cell injury. Increased beclin 1 expression, however, has been consistently identified in myocardial ischemia/reperfusion. Because of the role of nitric oxide (NO) in myocardial ischemia/reperfusion as well as in heart failure, we sought to determine whether NO and its byproduct peroxynitrite alter the expression of some genes involved in autophagy in the heart. Neonatal mouse cardiomyocytes were treated with SIN-1 (3-morpholinosydnonimine), which releases NO and accelerates formation of peroxynitrite. Gene expression was evaluated using RNA labeled and hybridized to cDNA microarrays. SIN-1 treatment induced significant changes in five caspases. In contrast, there were no changes in three genes involved in autophagy, namely beclin 1, Atg5l and Atg12l. Several different time periods were examined; a short time period, 2h, to more closely model myocardial ischemia reperfusion and a long time period, 20 h, that more closely represents sustained injury. In summary, evidence to date suggests that NO is not involved in increased beclin 1 expression in ischemia/reperfusion injury in the heart and would be unlikely to account for the signs of autophagy in the hearts of patients with heart failure.
- Subjects :
- Animals
Animals, Newborn
Apoptosis drug effects
Apoptosis Regulatory Proteins
Beclin-1
Caspases genetics
Cell Death drug effects
DNA, Complementary
Heart Failure physiopathology
Humans
Mice
Molsidomine analogs & derivatives
Molsidomine pharmacology
Myocardial Ischemia physiopathology
Myocardial Reperfusion Injury physiopathology
Myocytes, Cardiac cytology
Myocytes, Cardiac drug effects
Myocytes, Cardiac metabolism
Nitric Oxide pharmacology
Nitric Oxide Donors pharmacology
Oligonucleotide Array Sequence Analysis
Peroxynitrous Acid biosynthesis
Proteins genetics
Proteins metabolism
RNA metabolism
Time Factors
Autophagy genetics
Caspases metabolism
Gene Expression Regulation
Myocardium metabolism
Nitric Oxide metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1554-8627
- Volume :
- 3
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Autophagy
- Publication Type :
- Academic Journal
- Accession number :
- 17438363
- Full Text :
- https://doi.org/10.4161/auto.4054