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High altitude acclimatization responses in cerebral artery PKC‐dependent signaling pathway proteins: Changes with development
Author(s) -
Goyal Ravi,
Mittal Ashwani,
Shi Lijun,
Wedhas Nia,
Longo Lawrence D.
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.616.14
Subject(s) - protein kinase c , fetus , sensitization , myosin light chain kinase , hypoxia (environmental) , medicine , endocrinology , biology , cerebral arteries , signal transduction , myosin , acclimatization , myosin light chain phosphatase , microbiology and biotechnology , anatomy , chemistry , neuroscience , oxygen , pregnancy , botany , organic chemistry , genetics
Objective High altitude, long‐term hypoxia (LTH) is associated with a number of changes in pre‐ and post‐junctional signaling in both fetal and adult cerebrovasculature. Because PKC and downstream pathways play a key role in Ca 2+ sensitization of vascular contraction, and are less abundant in fetus, we tested the hypothesis that LTH alters PKC activation pathways differently in the fetus, as compared to the adult. Methods In cerebral arteries we quantified both total and activated (phosphorylated) PKC, ERK1/2, caldesmon, Rho A, CPI‐17, and myosin light chain 20 (MLC 20 ), and PDBu‐ (PKC agonist) induced contractions and their responses to blockade of ERKs (U‐0126) or Rho kinase (Y‐27632). Results In adult cerebral arteries, LTH acclimatization was associated with significant decreases in total and activated PKC, with increases in activated ERK1/2, CPI‐17, and MLC 20 and its kinase. In contrast, in fetal arteries LTH increased PKC expression and increased ERK1/2 activation, with no change in caldesmon, Rho A, CPI‐17, or MLC 20 . Conclusions In adult cerebral arteries, acclimatization to LTH is associated with significant up‐ or down‐regulation of a number of elements of the PKC‐dependent Ca 2+ sensitization pathway. In contrast, acclimatization to LTH in the fetus is associated with relatively minor changes in the Ca 2+ sensitization pathway. (Supported by USPHS HD 31226)