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CRYAB and HSPB2 deficiency increases myocyte mitochondrial permeability transition and mitochondrial calcium uptake. J Mol Cell Cardiol 2006 Jun;40(6):783-9

Date

05/09/2006

Pubmed ID

16678848

DOI

10.1016/j.yjmcc.2006.03.003

Scopus ID

2-s2.0-33744541387   50 Citations

Abstract

Double knockout (DKO) of the small heat shock proteins CRYAB and HSPB2 increases necrosis and apoptosis induced by ischemia/reperfusion (I/R) in vitro, but the mechanisms involved are unknown. We examined [Ca2+]i during metabolic inhibition (MI) changes in [Ca2+]m induced by exposure to elevated [Ca2+]i, and whether mitochondria in isolated DKO ventricular myocytes (VM) are more susceptible than wild type (WT) to induction of the mitochondrial permeability transition (MPT). The rise in [Ca2+]i in DKO myocytes during metabolic inhibition (MI) was less than in WT, and ouabain caused a greater increase in [Ca2+]m in DKO than in WT. These findings suggested that Ca2+ uptake was increased in mitochondria in DKO myocytes. Measurements of Rhod 2 fluorescence during exposure of permeabilized VM to 1000 nM [Ca2+] for 5 min confirmed that DKO myocytes have enhanced mitochondrial Ca2+ uptake, and this difference between DKO and WT myocyte mitochondria was eliminated by inhibition of NO synthesis. MPT was induced more readily by ouabain, PAO, or TMRM in DKO myocytes than in WT. Thus, Ca2+ uptake by mitochondria is increased in DKO VM by a NO-dependent mechanism. This can predispose to the development of MPT, and increased VM injury during I/R. These findings indicate an important role of CRYAB and/or HSPB2 in mitochondrial function.

Author List

Kadono T, Zhang XQ, Srinivasan S, Ishida H, Barry WH, Benjamin IJ

Author

Ivor J. Benjamin MD Center Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Arsenicals
Calcium
Calcium Signaling
HSP27 Heat-Shock Proteins
Heat-Shock Proteins
Intracellular Membranes
Mice
Mitochondria, Heart
Myocytes, Cardiac
Nitric Oxide
Ouabain
Permeability
Rhodamines
Time Factors
alpha-Crystallin B Chain
jenkins-FCD Prod-482 91ad8a360b6da540234915ea01ff80e38bfdb40a