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Decreased eNOS activity induced by prenatal hypoxia results from abnormal interactions between eNOS and its regulatory proteins in adult sheep pulmonary arteries
Author(s) -
Liu Jie,
Gao Yuansheng,
Negash Sewite,
Tian Jia,
Longo Lawrence D,
Raj J. Usha
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1209.18
Subject(s) - enos , medicine , hypoxia (environmental) , endocrinology , heat shock protein , calmodulin , biology , chemistry , nitric oxide , biochemistry , calcium , nitric oxide synthase , oxygen , organic chemistry , gene
We previously reported that prenatal hypoxia resulted in persistent abnormalities in endothelium‐dependent relaxation responses of pulmonary arteries in adult sheep associated with unchanged eNOS protein expression but decreased eNOS activity (Faseb J. 21:A1203, 2007). To further elucidate the mechanisms responsible for the impairment of eNOS activity induced by prenatal hypoxia, we examined the regulatory proteins of eNOS and their interactions with eNOS by immunoprecipitation and immunoblotting analysis. Our results demonstrated that protein expression of caveolin–1, calmodulin and heat shock protein 90 did not change in prenatally hypoxic pulmonary arteries compared to controls. However, the interaction between eNOS and caveolin–1 was significantly increased, indicating that eNOS was tightly coupled with caveolin–1. The interactions of eNOS with calmodulin and heat shock protein 90 were greatly decreased, indicating that eNOS was dissociated from calmodulin and heat shock protein 90. Furthermore, phosphorylation of Ser 1177 and dephosphorylation of Thr495 of eNOS were significantly decreased in prenatally hypoxic pulmonary arteries, indicating that activation of eNOS was decreased. In conclusion, prenatal hypoxia impairs normal coupling between eNOS and its regulatory proteins and results in decreased eNOS activity. (Grants: NHLBI # HL 059435 and HL 075187).