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

• Published in: Biochemical and biophysical research communications Vol. 440; no. 4; pp. 696 - 700
• Main Authors: Wang, Xianwei, Dai, Yao, Ding, Zufeng, Khaidakov, Magomed, Mercanti, Federico, Mehta, Jawahar L.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.11.2013
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Angiotensin II; Angiotensin II - pharmacology; Angiotensin II - physiology; Animals; Anoxia; Apoptosis; Apoptosis Regulatory Proteins - metabolism; Autophagy; Beclin-1; Cell Hypoxia; Cell Line; Heat-Shock Proteins - metabolism; HL-1 cardiomyocytes; Mice; Microtubule-Associated Proteins - metabolism; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - physiology; Receptor, Angiotensin, Type 1 - metabolism; Receptor, Angiotensin, Type 2 - metabolism; Sequestosome-1 Protein; HL-1 cardiomyocytes; Anoxia; Angiotensin II; Autophagy; Apoptosis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.09.131

•Autophagy is an early and apoptosis a late response during anoxia.•Upon exposure to Ang II, autophagy occurs early and apoptosis late.•Apoptosis is mediated by activation of Ang II type 1 and type 2 receptors.•Autophagy is mediated solely by type 1 receptor activation. 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. 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. 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.