Beta(2)-adrenoceptor stimulation enhances latent transforming growth factor-beta-binding protein-1 and transforming growth factor-beta1 expression in rat hippocampus after transient forebrain ischemia.

Institut fuer Pharmakologie und Toxikologie, Philipps-Universitaet, Marburg, Germany. zhu@mailer.uni-marburg.de
A protective capacity of transforming growth factor-beta1 (TGF-beta1) against various insults inducing neurone cell death in vitro and in vivo has been well established. We have recently shown the rapid up-regulation and persistent expression of TGF-beta1 in surviving CA1 pyramidal cells after cerebral ischemia suggesting an endogenous mechanism of neuroprotection by this multifunctional cytokine. In the present study, we demonstrated that intraperitoneal administration of clenbuterol, a lipophilic beta(2)-adrenoceptor agonist, caused an increase in TGF-beta1 expression in non-ischemic rats and further enhanced TGF-beta1 protein levels in rat CA1 pyramidal neurones after transient forebrain ischemia. In the hippocampus neuroprotection by clenbuterol (0.5 mg/kg) was accompanied by increased TGF-beta1 immunoreactivity as early as 3 h, and remained elevated up to 2 days after ischemia. The corresponding increased TGF-beta1 mRNA levels after ischemia were not further enhanced by clenbuterol, suggesting post-transcriptional regulation of TGF-beta1 protein after beta(2)-adrenoceptor stimulation. In saline-treated rats latent TGF-beta-binding protein-1 (LTBP-1) immunoreactivity was moderately elevated 3 and 6 h after ischemia, and returned to control levels after 1 day of reperfusion. In parallel with the up-regulation of TGF-beta1 immunoreactivity, LTBP-1 levels in the hippocampus were considerably increased by clenbuterol from 3 h to 2 days after ischemia. Our data demonstrate a concomitant increase in LTBP-1 and TGF-beta1 expression in the ischemic hippocampus after stimulation of beta(2)-adrenoceptors.
Mesh Terms:
Adrenergic beta-Agonists, Animals, Carrier Proteins, Clenbuterol, Gene Expression, Hippocampus, Intracellular Signaling Peptides and Proteins, Ischemic Attack, Transient, Latent TGF-beta Binding Proteins, Male, RNA, Messenger, Rats, Rats, Wistar, Receptors, Adrenergic, beta-2, Transforming Growth Factor beta, Transforming Growth Factor beta1
Neuroscience Nov. 27, 2001; 107(4);593-602 [PUBMED:11720783]
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