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.
Zhu
Y
Y
Institut für Pharmakologie und Toxikologie, Philipps-Universität, Marburg, Germany. zhu@mailer.uni-marburg.de
Culmsee
C
C
Roth-Eichhorn
S
S
Krieglstein
J
J
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics*; D002976:Clenbuterol / Q000494:pharmacology; D015870:Gene Expression / Q000502:physiology; D006624:Hippocampus / Q000098:blood supply / Q000737:chemistry / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000503:physiopathology*; D053779:Latent TGF-beta Binding Proteins; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics*; D053773:Transforming Growth Factor beta1
D000318:Adrenergic beta-Agonists; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D053779:Latent TGF-beta Binding Proteins; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D002976:Clenbuterol