当前位置： SCI文献检索 > JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY期刊下所有文献 > Genetic modification of the heart: chaperones and the cytoskeleton.

Genetic modification of the heart: chaperones and the cytoskeleton.

Abstract：

:In the past decade, genetic modification has been extensively employed to define (patho)physiological roles of chaperones and the cytoskeleton in the heart, promoting dramatic advances in this field. Both loss-of-function and gain-of-function approaches have been used productively. alphaB-Crystallin (CryAB) is the most abundant small heat shock protein (HSP) in the heart. A missense mutation (R120G) in CryAB that is linked to human desmin-related myopathy (DRM), has proved in transgenic (TG) mice to be causative, likely through compromising the function of both CryAB and desmin filaments and inducing aberrant protein aggregation. For the molecular chaperones, the consensus gained is that up-regulation of each of the HSPs in the heart is protective against insults such as ischemia/reperfusion (I/R) injury. CryAB modulates protein aggregation of abnormal desmin. With respect to the cytoskeleton, disruption of the non-sarcomeric actin linkage at the intercalated discs via overexpressing the VASP-EHV1 domain is sufficient to cause dilated cardiomyopathy (DCM). Up-regulation of microtubule-associated protein 4 (MAP4) results in microtubule densification. Myocyte contractile malfunction characteristic of pressure overload hypertrophy is recapitulated by cardiac-restricted overexpression of MAP4. In contrast, overexpression of desmin filaments by itself is not detrimental to the heart. Although loss-of-function studies have been more limited, ablation of the desmin gene causes mitochondrial dysfunction and apoptosis, resulting in cardiomyopathy in mice. From function studies, abnormal desmin aggregation and disruption of the desmin networks resulting from expression of either mutant desmin or mutant CryAB have been shown to remodel the heart and compromise cardiac function, suggesting their synergistic roles in disease pathogenesis.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Kumarapeli AR,Wang X

doi

10.1016/j.yjmcc.2004.07.004

keywords:

subject

Has Abstract

pub_date

2004-12-01 00:00:00

pages

1097-109

issue

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(04)00229-9

journal_volume

pub_type

杂志文章,评审

在线工具

Genetic modification of the heart: chaperones and the cytoskeleton.