Differential expression of small heat shock proteins in reactive astrocytes after focal ischemia: possible role of beta-adrenergic receptor.
Small heat shock proteins (sHSPs), a family of HSPs, are known to accumulate in the CNS, mainly in astrocytes, in several pathological conditions such as Alexander's disease, Alzheimer's disease, and Creutzfeldt-Jakob disease. sHSPs may act not only as molecular chaperones, protecting against various stress stimuli, but may also play a physiological role in regulating cell differentiation and proliferation. In the present study, we have demonstrated that transient focal ischemia in rats dramatically induced HSP27 but not alpha B-crystallin (alphaBC), both of which are members of sHSPs, in reactive astrocytes. In contrast, in vitro chemical ischemic stress induced both HSP27 and alphaBC in cultured glial cells to the same extent. Dibutyryl cAMP (dBcAMP) and isoproterenol, a beta-adrenergic receptor (betaAR) agonist, enhanced HSP27 expression but suppressed alphaBC, and changed the shape of the cells to a stellate form. dBcAMP and isoproterenol inhibited cell proliferation under normal conditions. An increase in betaAR-like immunoreactivity was also observed in reactive astrocytes in vivo. These results, together with recent findings that betaAR plays an important role in glial scar formation in vivo, raise the possibility that betaAR activation modulates sHSP expression after focal ischemia and is involved in the transformation of astrocytes to their reactive form.
Imura
T
T
Department of Neurology, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Shimohama
S
S
Sato
M
M
Nishikawa
H
H
Madono
K
K
Akaike
A
A
Kimura
J
J
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D003459:Crystallins / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D015424:Reperfusion
D003459:Crystallins; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D011943:Receptors, Adrenergic, beta; D003994:Bucladesine; D007545:Isoproterenol