Caveolin-3 plays a critical role in autophagy after ischemia-reperfusion

Kassan, Adam, Pham, Uyen, Quynhmy Nguyen, Reichelt, Melissa E., Cho, Eunbyul, Patel, Piyush M., Roth, David M., Head, Brian P. and Patel, Hemal H. (2016) Caveolin-3 plays a critical role in autophagy after ischemia-reperfusion. American Journal of Physiology - Cell Physiology, 311 6: C854-C865. doi:10.1152/ajpcell.00147.2016

Author Kassan, Adam
Pham, Uyen
Quynhmy Nguyen
Reichelt, Melissa E.
Cho, Eunbyul
Patel, Piyush M.
Roth, David M.
Head, Brian P.
Patel, Hemal H.
Title Caveolin-3 plays a critical role in autophagy after ischemia-reperfusion
Journal name American Journal of Physiology - Cell Physiology   Check publisher's open access policy
ISSN 1522-1563
Publication date 2016-12-01
Sub-type Article (original research)
DOI 10.1152/ajpcell.00147.2016
Open Access Status Not yet assessed
Volume 311
Issue 6
Start page C854
End page C865
Total pages 12
Place of publication Bethesda, MD, United States
Publisher American Physiological Society
Language eng
Subject 1314 Physiology
1307 Cell Biology
Abstract Autophagy is a dynamic recycling process responsible for the breakdown of misfolded proteins and damaged organelles, providing nutrients and energy for cellular renovation and homeostasis. Loss of autophagy is associated with cardiovascular diseases. Caveolin-3 (Cav-3), a muscle-specific isoform, is a structural protein within caveolae and is critical to stress adaptation in the heart. Whether Cav-3 plays a role in regulating autophagy to modulate cardiac stress responses remains unknown. In the present study, we used HL-1 cells, a cardiac muscle cell line, with stable Cav-3 knockdown (Cav-3 KD) and Cav-3 overexpression (Cav-3 OE) to study the impact of Cav-3 in regulation of autophagy. We show that traditional stimulators of autophagy (i.e., rapamycin and starvation) result in upregulation of the process in Cav-3 OE cells while Cav-3 KD cells have a blunted response. Cav-3 coimmunoprecipitated with beclin-1 and Atg12, showing an interaction of caveolin with autophagy-related proteins. In the heart, autophagy may be a major regulator of protection from ischemic stress. We found that Cav-3 KD cells have a decreased expression of autophagy markers [beclin-1, light chain (LC3-II)] after simulated ischemia and ischemia-reperfusion (I/R) compared with WT, whereas OE cells showed increased expression. Moreover, Cav-3 KD cells showed increased cell death and higher level of apoptotic proteins (cleaved caspase-3 and cytochrome c) with suppressed mitochondrial function in response to simulated ischemia and I/R, whereas Cav-3 OE cells were protected and had preserved mitochondrial function. Taken together, these results indicate that autophagy regulates adaptation to cardiac stress in a Cav-3-dependent manner.
Keyword Mitochondria
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID I01 BX000783
P01 HL066941
R01 HL091071
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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