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.
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
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
Date: Nov. 27, 2001
PubMed ID: 11720783
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