Hsp90 mediates the balance of nitric oxide and superoxide anion in the lungs of rats with acute pulmonary thromboembolism.
Acute pulmonary thromboembolism (PTE) can result in serious vascular responses. The association of heat shock protein 90 (Hsp90) with endothelial nitric oxide synthase (eNOS), which generates nitric oxide (NO) and superoxide anion (O2(-)), is a critical mechanism on regulating vessel homeostasis. In this study, the role of Hsp90 association with eNOS in the balance of NO and O2(-) was examined in PTE rat model. PTE rats model was induced by intrajugular injection of autologous blood clots (0.04 g/kg), lung homogenate was collected at appointed time length to assess NO production and O2(-) production. The interaction of Hsp90 and eNOS protein in every group was detected. Treatment of PTE model rats with geldanamycin, a commonly used Hsp90 inhibitor, augmented eNOS phosphorylation at Thr-495, depressing eNOS activity. Together with the increase of NO production in lung homogenate of PTE rats at 1 h and its maximum reached at 3 d, geldanamycin treatment significantly attenuated the production of NO but augmented the production of O2(-) in the lungs of rats after PTE at indicated time length. These results suggest that geldanamycin may enhance eNOS phosphorylation at Thr-495 by inhibiting Hsp90, Hsp90 uncoupling eNOS protein results in increased eNOS-dependent O2(-) production.
Key Lab of Pulmonary Diseases of Ministry of Health, Department of Respiratory Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Xiaoju
X
Zhang
Yang
Y
Jin
Lei
L
Xia
Xiaonan
X
Tao
Ming
M
Bai
Jianchu
J
Zhang
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D018841:HSP90 Heat-Shock Proteins / Q000502:physiology*; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008168:Lung / Q000378:metabolism*; D008297:Male; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis / Q000235:genetics; D011655:Pulmonary Embolism / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D018841:HSP90 Heat-Shock Proteins; D009566:Nitrates; D013481:Superoxides; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III