title: Heat shock protein 90 regulates stabilization rather than activation of soluble guanylate cyclase.
abstract: Endothelium-derived nitric oxide (NO) activates the heterodimeric heme protein soluble guanylate cyclase (sGC) to form cGMP. In different disease states, sGC levels and activity are diminished possibly involving the sGC binding chaperone, heat shock protein 90 (hsp90). Here we show that prolonged hsp90 inhibition in different cell types reduces protein levels of both sGC subunits by about half, an effect that was prevented by the proteasome inhibitor MG132. Conversely, acute hsp90 inhibition affected neither basal nor NO-stimulated sGC activity. Thus, hsp90 is a molecular stabilizer for sGC tonically preventing proteasomal degradation rather than having a role in short-term activity regulation.
authors.affiliation: Rudolf-Buchheim-lnstitute for Pharmacology, University of Giessen, Germany.
authors.forename: Pavel I
authors.initials: PI
authors.lastname: Nedvetsky
authors.forename: Sabine
authors.initials: S
authors.lastname: Meurer
authors.forename: Nils
authors.initials: N
authors.lastname: Opitz
authors.forename: Tatiana Y
authors.initials: TY
authors.lastname: Nedvetskaya
authors.forename: Helmut
authors.initials: H
authors.lastname: Müller
authors.forename: Harald H H W
authors.initials: HH
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D019281:Dimerization; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D016716:PC12 Cells; D051381:Rats; D018411:Spodoptera
chemical_list: D018841:HSP90 Heat-Shock Proteins; D006162:Guanylate Cyclase; D006152:Cyclic GMP