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Hydrogen Peroxide Induced Calcium Mobilization in Pulmonary Arterial Smooth Muscle Cells (PASMCs)
Author(s) -
Lin MoJun,
Yang XiaoRu,
Sham James S.K.
Publication year - 2006
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.20.4.a400-a
Subject(s) - hypoxic pulmonary vasoconstriction , ryanodine receptor , reactive oxygen species , chemistry , nifedipine , vasoconstriction , calcium , extracellular , calcium signaling , medicine , vascular smooth muscle , trpc6 , endocrinology , microbiology and biotechnology , signal transduction , biophysics , receptor , transient receptor potential channel , biochemistry , biology , organic chemistry , smooth muscle
Reactive oxygen species (ROS) generate from NADPH oxidases and mitochondria have been implicated as signaling molecules for pulmonary vasoconstriction and cell proliferation induced by agonists, and acute/chronic hypoxia. Since Ca 2+ mobilization is essential for both vasoconstriction and cell proliferation, we sought to characterize the Ca 2+ response activated by H 2 O 2 in rat PASMCs. Exogenous application of 10 μM to 1 mM H 2 O 2 elicited concentration‐dependent increase in [Ca 2+] i, with an initial rise followed by a slow secondary Ca 2+ increase. The initial phase persisted in Ca 2+ ‐free solution, but was significantly attenuated by the IP 3 receptor antagonist 2‐APB and/or ryanodine. In contrast, the secondary phase was dependent on extracellular Ca 2+ . But, it was unaffected by nifedipine, SK&F 96365 or La 3+ . Moreover, Mn 2+ quenching of fura‐2 was unaltered by H 2 O 2 , suggesting that non‐selective cation channels were not involved. However, inhibition of Na + ‐Ca 2+ exchange using millimolar Ni 2+ significantly attenuated the secondary Ca 2+ increase. These results suggest that multiple Ca 2+ pathways, including IP 3 ‐ and ryanodine receptor‐gated Ca 2+ stores, and Na + ‐Ca 2+ exchange, participate in the Ca 2+ transient induced by H 2 O 2 , and they may play an important role in ROS signaling in pulmonary vasculature.