The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress (Nat Med, 2007, 13:619-624)

報告日期: 2007/11/20
報告時間: 17:10/18:00
報告學生: 張程翔
講評老師: 簡基憲
附件下載:

http://basicmed.med.ncku.edu.tw/upload_data/961120-3.pdf

 

The role of autophagy in cardiomyocytes in the basal state and in response to hemodynamic stress

Nature Medicine 13, 619 - 624 (2007)

 

Speaker: Cherng-Shyang Chang

Commentator: Dr. Chi-Hsien Chien

Date: 11/20/2007 17:00~ 18:00

Place: Room 602

 

Abstract:

Autophagy, like the dustcart, recycles the material in cytoplasm. Previously, it has been shown that autophagy plays a beneficial role in starving cells associated with the mechanism of cell survival. However, autophagy has also been found in various heart diseases, including cardiac hypertrophy and heart failure. To understand the precise role of autophagy in heart, Atg5, a critical molecule for autophagy elongation, has been knocked out by Cre-LoxP system in mice. The temporally controlled cardiac-specific Atg5-deficient mice were generated, and controlled by administration of Tamoxifen. Loss of Atg5 caused cardiomyopathy characterized the cardiac hypertrophy, left ventricular dilatation and contractile dysfunction, accompanied with increased levels of ubiquitination. Ultrastructural analysis of Atg5-deficient hearts revealed a disorganized sarcomere structure, misalignment and aggregation of mitochondria. In addition, the author also generated cardiac-specific Atg5-deficient mice, which loss Atg5 in heart before birth. In contrast, loss the autophagy early at embryonic stage showed normal cardiac phenotype in the basal state, but relapsed under pressure overload. These results suggest that constitutive autophagy is beneficial for heart to maintain cardiomyocyte size, global cardiac structure and organ function in basal stage, and controls the adaptive response in failing heart to protect cells from hemodynamic stress.

 

Reference:

1.     Mizushima, N., Ohsumi, Y. & Yoshimori, T. Autophagosome formation in mammalian cells. Cell Struct. Funct. 27, 421–429 (2002).

2.     Zhu, H., Tannous, P., Johnstone, JL., Kong, Y., Shelton, JM., Richardson, JA., Le, V., Levine, B., Rothermel, BA., Hill, JA. Cardiac autophagy is a maladaptive response to hemodynamic stress. 2007 J Clin Invest. 117, 1782-1793 (2007)