Heat shock protein 90 regulates stabilization rather than activation of soluble guanylate cyclase |
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Authors: | Nedvetsky Pavel I Meurer Sabine Opitz Nils Nedvetskaya Tatiana Y Müller Helmut Schmidt Harald H H W |
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Affiliation: | Rudolf-Buchheim-lnstitute for Pharmacology, University of Giessen, Germany. |
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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. |
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Keywords: | cGMP, cyclic GMP eNOS, endothelial NO synthase GA, geldanamycin hsp90, heat shock protein 90 NO, nitric oxide PPAECs, porcine pulmonary artery endothelial cells RD, radicicol sGC, soluble guanylate cyclase SMCs, smooth muscle cells |
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