Premium
Intrauterine hypoxia inhibits caspase 3 in a NO‐dependent manner in fetal hearts
Author(s) -
Evans LaShauna,
Liu Hongshan,
Thompson Loren P
Publication year - 2009
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.23.1_supplement.807.10
Subject(s) - hypoxia (environmental) , fetus , apoptosis , medicine , endocrinology , caspase 3 , guinea pig , miniature pig , andrology , nitric oxide , biology , chemistry , programmed cell death , oxygen , biochemistry , pregnancy , organic chemistry , genetics
Nitric oxide (NO) is an important regulator of cardiac function and apoptosis. We have previously shown that hypoxia upregulates iNOS expression in fetal guinea pig hearts. Thus, the aim of this study is to quantify the effect of intrauterine hypoxia on the pro‐apoptotic enzyme, caspase 3, and the role of NO in fetal hearts. Methods To test this pregnant guinea pigs were exposed to room air (N=4) or 10.5%O 2 (N=5) for 14d prior to term (term=65d) and administered either water or L‐NIL, a selective iNOS inhibitor, at 1‐2mg/kg/d for 7‐10d. At 60d gestation, near term fetuses were removed from anesthetized sows, fetal hearts excised, and left ventricles frozen in liquid N 2 and stored in − 80C. Caspase 3 protein and activity levels were measured by Western and ELISA kit, respectively. Results Chronic HPX decreased (P=.009) active caspase 3 (15kDa) protein levels by 40%, but had no effect on either levels of the pro‐form (32kDa) or active caspase 3 form (22kDa) compared to NMX controls. Hypoxia decreased (P=.029) activity levels by 38% compared to NMX controls. L‐NIL reversed the HPX‐induced decrease and increased activity levels by 72% compared to HPX alone. Thus, chronic hypoxia inhibits apoptosis in near term fetal guinea pig hearts. This may be mediated by an inhibitory effect of NO on caspase 3 activity as a compensatory and cardioprotective response to hypoxic stress. [(NIH HL49999/LT & NIH HL90044/LE)]