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

Neuroscience. 2001;107(4):593-602. doi: 10.1016/s0306-4522(01)00357-8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Carrier Proteins / analysis
  • Carrier Proteins / genetics*
  • Clenbuterol / pharmacology
  • Gene Expression / physiology
  • Hippocampus / blood supply
  • Hippocampus / chemistry
  • Hippocampus / physiology*
  • Intracellular Signaling Peptides and Proteins*
  • Ischemic Attack, Transient / drug therapy
  • Ischemic Attack, Transient / physiopathology*
  • Latent TGF-beta Binding Proteins
  • Male
  • RNA, Messenger / analysis
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, beta-2 / metabolism*
  • Transforming Growth Factor beta / analysis
  • Transforming Growth Factor beta / genetics*
  • Transforming Growth Factor beta1


  • Adrenergic beta-Agonists
  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • Latent TGF-beta Binding Proteins
  • RNA, Messenger
  • Receptors, Adrenergic, beta-2
  • Tgfb1 protein, rat
  • Transforming Growth Factor beta
  • Transforming Growth Factor beta1
  • Clenbuterol