       Document 0764
 DOCN  M9610764
 TI    Some new aspects of molecular mechanisms of cyclosporin A effect on
       immune response.
 DT    9601
 AU    Zav'yalov VP; Denesyuk AI; Lundell J; Korpela T; Institute of
       Immunology, Lyubuchany, Moscow Region, Russia.
 SO    APMIS. 1995 Jun;103(6):401-15. Unique Identifier : AIDSLINE MED/96028031
 AB    A few protein targets were found to display a specific high-affinity
       interaction with the immunosuppressant cyclosporin A (CsA): cytosolic
       cyclophilins (CyP)A, B, C, D, E containing from 122 to 174 amino acid
       residues in a polypeptide chain, and secreted forms of CyP; CyP-40,
       40-kDa CsA-binding polypeptide complexed with steroid receptor (SR);
       CyP-related 150-kDa receptor of natural killer (NK) cells; interleukin 8
       (IL-8); actin; a family of molecular chaperones hsp70 and P-glycoprotein
       (P-GP). All CyPs possess peptidyl-prolyl cis-trans isomerase activity
       (PPIase) and may serve as ATP-independent molecular chaperone proteins.
       The CsA-CyP complexes are specific inhibitors of Ca(2+)-and
       calmodulin-dependent protein phosphatase calcineurin (CaN). The
       inhibition of CaN blocks the activation of genes of IL-2, IL-2R, IL-4,
       etc. in T cells. In addition, immunosuppressive and/or antiinflammatory
       activity of CsA can be executed via CyP-40 and hsp 70 complexed with SR,
       and following the interaction with CyP-related receptor of NK and with
       IL-8. CsA binding to CyPC, P-GP and actin may throw light on the
       biochemical events leading to nephrotoxicity and graft vessel disease,
       two major side effects produced by CsA. The discovery of the interaction
       of human immunodeficiency virus type 1 (HIV-1) Gag protein with CyP and
       effective disruption of this interaction by CsA may be important for our
       understanding of the pathology caused by this immunosuppressive virus
       and will inspire therapeutic strategies to nip HIV in the bud. Bacterial
       immunophilins (ImPs) contribute to the virulence of pathogenic
       microorganisms. Elucidation of molecular mechanisms of microbial ImPs'
       action in the pathogenesis of bacterial infections may lead to new
       strategies for designing antibacterial drugs.
 DE    Actins/METABOLISM  Calmodulin-Binding Proteins/METABOLISM  Carrier
       Proteins/METABOLISM  Cyclosporine/*METABOLISM/PHARMACOLOGY  DNA-Binding
       Proteins/METABOLISM  Heat-Shock Proteins/METABOLISM  Heat-Shock Proteins
       70/METABOLISM  Human  Immunity/*DRUG EFFECTS  Immunosuppressive
       Agents/*PHARMACOLOGY  Interleukin-8/METABOLISM
       P-Glycoprotein/METABOLISM  Phosphoprotein Phosphatase/METABOLISM
       JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

