Journal article
Mechanism of Increased Tyrosine (Tyr99) Phosphorylation of Calmodulin During Hypoxia in the Cerebral Cortex of Newborn Piglets: The Role of nNOS-Derived Nitric Oxide
Neurochemical research, v 35(1)
2010
PMID: 19590958
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The present study aims to investigate the mechanism of calmodulin modification during hypoxia and tests the hypothesis that hypoxia-induced increase in Tyr
99
phosphorylation of calmodulin in the cerebral cortex of newborn piglets is mediated by NO derived from nNOS. Fifteen piglets were divided into normoxic (Nx,
n
= 5), hypoxic (Hx, F
i
O
2
of 0.07 for 1 h,
n
= 5) and hypoxic-pretreated with nNOSi (Hx-nNOSi,
n
= 5) groups. nNOS inhibitor I (selectivity >2,500 vs. eNOS and >500 vs. iNOS) was administered (0.4 mg/kg, I.V.) 30 min prior to hypoxia. Cortical membranes were isolated and tyrosine phosphorylation (Tyr
99
and total) of calmodulin determined by Western blot using anti-phospho-(pTyr
99
)-calmodulin and anti-pTyr antibodies. Protein bands were detected by enhanced chemiluminescence, analyzed by densitometry and expressed as absorbance. The pTyr
99
calmodulin (ODxmm
2
) was 78.55 ± 10.76 in Nx, 165.05 ± 12.26 in Hx (
P
< 0.05 vs. Nx) and 96.97 ± 13.18 in Hx-nNOSi (
P
< 0.05 vs. Hx,
P
= NS vs. Nx). Expression of total tyrosine phosphorylated calmodulin was 69.24 ± 13.69 in Nx, 156.17 ± 16.34 in Hx (
P
< 0.05 vs. Nx) and 74.18 ± 3.9 in Hx-nNOSi (
P
< 0.05 vs. Hx,
P
= NS vs. Nx). The data show that administration of nNOS inhibitor prevented the hypoxia-induced increased Tyr
99
phosphorylation of calmodulin. Total tyrosine phosphorylation of calmodulin was similar to Tyr
99
phosphorylation. We conclude that the mechanism of hypoxia-induced modification (Tyr
99
phosphorylation) of calmodulin is mediated by NO derived from nNOS. We speculate that Tyr
99
phosphorylated calmodulin, as compared to non-phosphorylated, binds with a higher affinity at the calmodulin binding site of nNOS leading to increased activation of nNOS and increased generation of NO.
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Details
- Title
- Mechanism of Increased Tyrosine (Tyr99) Phosphorylation of Calmodulin During Hypoxia in the Cerebral Cortex of Newborn Piglets: The Role of nNOS-Derived Nitric Oxide
- Creators
- Om Prakash Mishra - Drexel University College of Medicine and St. Christopher’s Hospital for ChildrenQazi M. Ashraf - Drexel University College of Medicine and St. Christopher’s Hospital for ChildrenMaria Delivoria-Papadopoulos - Drexel University
- Publication Details
- Neurochemical research, v 35(1)
- Publisher
- Springer US
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000273093800008
- Scopus ID
- 2-s2.0-76849100019
- Other Identifier
- 991019168681604721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Biochemistry & Molecular Biology
- Neurosciences