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Ischemic preconditioning: a potential role for constitutive low molecular weight stress protein translocation and phosphorylation?

Abstract：

:We have investigated whether translocation of constitutive low molecular weight stress proteins (alphaB-crystallin and HSP27) to the myofilament/cytoskeletal compartment occurs during ischemic preconditioning and assessed if this is causally associated with cardioprotection. Triton-insoluble preparations from fresh or aerobically perfused rat hearts (n=4/group) contained relatively little alphaB-crystallin (96 +/- 43 and 43 +/- 36 units respectively) or HSP27 (177 +/- 32 and 101 +/- 26 units respectively). Three preconditioning cycles of (5 min ischemia + 5 min reperfusion) increased the Triton-insoluble crystallin to 864 +/- 61 units (P<0.05) and HSP27 to 1353 +/- 53 units (P<0.05). Two hours of aerobic perfusion following the preconditioning protocol resulted the return of alphaB-crystallin and HSP27 to near control levels (189 +/- 14 units and 252 +/- 24 units, respectively). Stress protein translocation, comparable to that achieved by the IPC protocol was induced by aerobic perfusion with hypercarbic (pH 6.8) perfusion. Thus, three cycles of 5 min hypercarbia + 5 min normocarbia increased alphaB-crystallin to 628 +/- 30 units (P<0.05) and HSP27 to 1353 +/- 53 units. In parallel functional studies, the recovery of LVDP after 35 min ischemia and 60 min of reperfusion was 43 +/- 7% in the ischemic control group, 61 +/- 3% (P<0.05) in the preconditioned group and 42 +/- 6% in the hypercarbic group. Thus, translocation of alphaB-crystallin and/or is not of-itself sufficient to induce cardioprotection. Using a phospho-specific antibody, we have demonstrated that preconditioning not only translocates alphaB-crystallin but also increases its phosphorylation at Ser-59 by 9.7-fold compared to aerobic controls (1616 +/- 402 v 166 +/- 28 units respectively). In contrast, hypercarbia while eliciting a comparable translocation, failed to alter the phosphorylation state of alphaB-crystallin. Preconditioning-induced phosphorylation was significantly attenuated by 50 microM genistein (by 61%), 10 microM SB203580 (by 91%) and 10 microM bisindolylmaleimide (by 68%), but not by 10 microM PD98059 (by 4%). Our findings are consistent with the possibility that ischemic preconditioning may be mediated by phosphorylation and translocation of constitutive low molecular weight stress proteins, particularly alphaB-crystallin.

journal_name

J Mol Cell Cardiol

journal_title

Journal of molecular and cellular cardiology

authors

Eaton P,Awad WI,Miller JI,Hearse DJ,Shattock MJ

doi

10.1006/jmcc.2000.1136

keywords:

subject

Has Abstract

pub_date

2000-06-01 00:00:00

pages

961-71

issue

eissn

0022-2828

issn

1095-8584

pii

S0022-2828(00)91136-2

journal_volume

pub_type

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Ischemic preconditioning: a potential role for constitutive low molecular weight stress protein translocation and phosphorylation?