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Regulation of autophagy and apoptosis in response to angiotensin II in HL-1 cardiomyocytes.

Abstract：

BACKGROUND:Autophagy and apoptosis are two important regulators of cell survival, and are often observed simultaneously in response to noxious stimuli. Anoxia is a known stimulus for autophagy and apoptosis, and angiotensin (Ang) II is a major mediator of anoxic injury. However, specific responses to anoxia and Ang II in terms of occurrence of autophagy and apoptosis have still not been delineated. METHODS AND RESULTS:We observed that autophagy (measured as LC3 staining, and Beclin-1 and p62 Western blotting) was an early response and apoptosis (measured as TUNEL staining, and Annexin V and Smac/Diablo Western blotting) became dominant as the duration of anoxia was prolonged. Autophagy also occurred quickly in response to low concentrations of Ang II. When exposed to high concentrations of Ang II, a significant number of cells developed apoptosis, while autophagy response decreased. Ang II-mediated apoptosis was blocked by Ang II type 1 receptor (AT1R) blocker losartan as well as by the AT2R blocker PD123319. Ang II-induced autophagy was blocked by losartan, but not by PD123319. CONCLUSION:Exposure to Ang II, a mediator of anoxic injury, initiates a rapid autophagy response, perhaps in an attempt to protect tissues from the impending noxious effects. However, when anoxia (and thereby release of Ang II) is prolonged, the process of apoptosis dominates. These processes will determine the outcome of cardiomyocyte well-being in states of hypoxia.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Wang X,Dai Y,Ding Z,Khaidakov M,Mercanti F,Mehta JL

doi

10.1016/j.bbrc.2013.09.131

subject

Has Abstract

pub_date

2013-11-01 00:00:00

pages

696-700

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(13)01636-7

journal_volume

440

pub_type

杂志文章

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