Enhanced Rotamase Activity of FK506-Binding Proteins within the Postischemic Brain
نویسنده
چکیده
Despite immunophilins being abundant in the brain,their functional role there remains unclear. Using rat models of transient focal cerebral ischemia,I investigated the effect of ischemic stress on the rotamase activity of immunophilins in the brain and examined the possible role of immunophilins in postischemic neuroprotection. I found that the rotamase activity of the FK506 binding protein class of immunophilins increases in response to ischemia and may play a key role in regulating the cascade of intracellular events after cerebral ischemia. This study provides direct evidence that the FK506 binding protein family of immunophilins mediate the neuroprotective effects of the immunosuppressant FK506 (tacrolimus) in the ischemic brain and suggests that a neuroprotective signal transduction system involving immunophilins could be used to treat ischemic stroke. (Jikeikai Med J 2003;50:9-14)
منابع مشابه
Neisseria meningitidis encodes an FK506-inhibitable rotamase.
Eukaryotic peptidyl-prolyl cis-trans isomerases (rotamases) fall into two classes, the cyclophilins inhibited by cyclosporin A and the FK506-binding proteins inhibited by the macrolide antibiotic FK506. In prokaryotes homologs of cyclophilins have been identified and found to have rotamase activity. Sequence similarities have been noted between FK506-binding proteins and gene products in a numb...
متن کاملNeurophilins and the nervous system.
Immunosuppressive drugs are being used increasingly to suppress rejection of organ transplants and to treat autoimmune disorders. Cyclosporin A (CsA), FK506, and rapamycin are among a class of immunosuppressants whose mechanisms of action are similar and which have unique neurological toxicity. Cyclosporin A and FK506 lack structural similarity yet have similar immunosuppressive effects, wherea...
متن کاملImmunophilin regulation of neurotransmitter release.
BACKGROUND The immunophilins are proteins that mediate actions of immunosuppressant drugs such as FK506 and cyclosporin A by binding to calcineurin, inhibiting its phosphatase activity, and increasing the phosphorylation level of transcription factors required for interleukin 2 formation. Though concentrations in the brain greatly exceed levels in immune tissues, no function has been previously...
متن کاملExpression, purification, and molecular characterization of Plasmodium falciparum FK506-binding protein 35 (PfFKBP35).
The immunosuppressive drug FK506 binds its targets FK506-binding protein (FKBP) family and modulates cellular processes. Recent studies demonstrated that FK506 shows anti-malaria effects. Newly identified FK506-binding protein 35 from Plasmodium falciparum (PfFKBP35) is assumed to be the molecular target of FK506 in the parasite. Currently, molecular and structural basis of growth inhibition of...
متن کاملA novel FK506- and rapamycin-binding protein (FPR3 gene product) in the yeast Saccharomyces cerevisiae is a proline rotamase localized to the nucleolus
The gene (FPR3) encoding a novel type of peptidylpropyl-cis-trans-isomerase (PPIase) was isolated during a search for previously unidentified nuclear proteins in Saccharomyces cerevisiae. PPIases are thought to act in conjunction with protein chaperones because they accelerate the rate of conformational interconversions around proline residues in polypeptides. The FPR3 gene product (Fpr3) is 41...
متن کامل