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Nitric oxide – mediated activation of ERK and JNK during hypoxia in neuronal nuclei of newborn pigs
Author(s) -
Miahra O. P.,
Ashraf Q. M.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.42_13.x
Subject(s) - mapk/erk pathway , kinase , nitric oxide , hypoxia (environmental) , phosphorylation , extracellular , chemistry , protein kinase a , c jun , endocrinology , medicine , microbiology and biotechnology , biology , biochemistry , oxygen , transcription factor , organic chemistry , gene
The extracellular signal‐regulated kinase (ERK) and c‐Jun N‐Terminal kinase (JNK) phosphorylate antiapoptotic proteins thereby may regulate hypoxia‐induced programmed cell death. The present study tests the hypotheses that hypoxia activates ERK and JNK in neuronal nuclei of newborn pigs and the hypoxa‐induced activation of ERK and JNK is mediated by nitric oxide (NO). Activated ERK and JNK were assessed by determining phosphorylated ERK and JNK by immunoblotting in 6 normoxic (Nx), 10 hypoxic (Hx) and 5 N‐nitro‐ l ‐arginine (a NOS inhibitor)‐treated (40 mg/kg) hypoxic (NNLA‐HX) 3–5‐day‐old‐piglets. Animals were exposed to an FiO 2 of 0.05–0.07 for 60 min Neuronal nuclei were isolated and nuclear proteins were immunoblotted with antiphosphorylated ERK and JNK. Protein bands were detected, analyzed and expressed as (OD × mm 2 ). Tissue hypoxia was documented by ATP levels. ATP levels were 4.45 ± 0.57, 1.16 ± 0.33 and 1.10 ± 0.25 µ m /g br in Nx, Hx ( p < 0.001 vs. Nx) and NNLA‐Hx ( p < 0.001 vs. Nx) groups, respectively. Phosphorylated ERK density was 170.5 ± 53.7 in Nx vs. 419.6 ± 63.9 in the Hx group ( p < 0.001) and 270.0 ± 28.7 in the NNLA‐Hx group ( p < 0.002 vs. Hx). Density of phosphorylated JNK was 172.8 ± 42.8 in the Nx vs. 364.6 ± 60.1 in the Hx ( p < 0.002 vs. Nx) and 254.8 ± 24.8 in the NNLA‐Hx group ( p < 0.002 vs. Hx). We data demonstrate increased activation of ERK and JNK following hypoxia. NNLA,a NOS inhibitor, decreased the hypoxia‐induced activation of ERK and JNK. We conclude that the hypoxia‐induced activation of ERK and JNK is NO‐mediated. Acknowledgements: Supported by NIH‐HD‐38079.