Functional Interdependence and Colocalization of Endothelial Nitric Oxide Synthase and Heat Shock Protein 90 in Cerebral Arteries
| Autor: | Vini G. Khurana, Daihiko Eguchi, Margaret J. Springett, Vijay H. Shah, Kristian Feterik, Zvonimir S. Katusic |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Cytoplasm
medicine.medical_specialty Nitric Oxide Synthase Type III Endothelium Lactams Macrocyclic Cerebral arteries Radioimmunoassay Uridine Triphosphate In Vitro Techniques 030218 nuclear medicine & medical imaging Hsp90 inhibitor Nitric oxide 03 medical and health sciences chemistry.chemical_compound Dogs 0302 clinical medicine Isometric Contraction Internal medicine Heat shock protein Benzoquinones polycyclic compounds medicine Animals HSP90 Heat-Shock Proteins Enzyme Inhibitors Microscopy Immunoelectron Cyclic GMP biology Quinones Geldanamycin Hsp90 Nitric oxide synthase NG-Nitroarginine Methyl Ester medicine.anatomical_structure Endocrinology Neurology chemistry Biochemistry Vasoconstriction Basilar Artery biology.protein Endothelium Vascular Neurology (clinical) Nitric Oxide Synthase Cardiology and Cardiovascular Medicine 030217 neurology & neurosurgery |
| Zdroj: | Journal of Cerebral Blood Flow & Metabolism. 20:1563-1570 |
| ISSN: | 1559-7016 0271-678X |
| DOI: | 10.1097/00004647-200011000-00006 |
| Popis: | Heat shock protein 90 (HSP90), an essential component of several signal transduction systems, participates in the activation of endothelial nitric oxide synthase (eNOS) in cells. The objective of the current study was to determine if HSP90 and eNOS were functionally interdependent and colocalized in the cerebral circulation. The authors used isometric force recording, cyclic 3′5′-guanosine monophosphate (cGMP) radioimmunoassay (RIA), and immunogold electron microscopy (EM) to study canine basilar artery. They found that geldanamycin (0.1 to 10 μg/mL), a selective HSP90 inhibitor, caused concentration-dependent contractions in arterial rings (n = 6 dogs). Contractions to geldanamycin were unaffected by a cyclooxygenase inhibitor, indomethacin (10 μmol/L; P < 0.05, n = 6). Functional evidence for interaction between HSP90 and nitric oxide (NO)-mediated signaling included observations that the contractile effect of geldanamycin was the following: (1) endothelium-dependent, (2) abolished by Ng-nitro-l-arginine methylester (L-NAME; 0.3 mmol/L), and (3) nonadditive with the contractile effect of this NOS inhibitor ( P < 0.01, n = 6 for each). Furthermore, RIA showed significant reduction in cGMP levels in arteries treated with geldanamycin (3 μg/mL; P < 0.02, n = 8), whereas immunogold EM demonstrated areas of colocalization of HSP90 and eNOS selectively in the cytoplasm of endothelial cells. The current findings suggest that in cerebral arteries, endothelial HSP90 plays an important role in modulation of basal NO-mediated signaling. This interaction may be particularly important in stress-induced up-regulation of HSP90 with subsequent alteration of vasomotor function. |
| Databáze: | OpenAIRE |
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