[Chronic hypoxia increases intracellular Ca(2+) concentration and augments proliferation by enhancing store-operated Ca(2+) entry in pulmonary arterial smooth muscle cells].
Zhonghua Nei Ke Za Zhi
; 55(9): 705-9, 2016 Sep 01.
Article
em Zh
| MEDLINE
| ID: mdl-27586979
ABSTRACT
OBJECTIVE:
To determine whether store-operated Ca(2+) entry (SOCE) is involved in chronic hypoxia-induced alteration of intracellular Ca(2+) concentration ([Ca(2+) ]i) and proliferation in pulmonary arterial smooth muscle cells (PASMC).METHODS:
Rat PASMCs were cultured and treated in normoxia (21%O2) or hypoxia (4%O2) condition. The proliferation of PASMC was detected by cell counting kit-8 (CCK-8) assay. [Ca(2+) ]i, SOCE and the effects of store-operated Ca(2+) channel (SOCC) inhibitors, SKF96365 and NiCl2, on SOCE in hypoxic PASMCs were tested by InCyte [Ca(2+) ]i measurement system.RESULTS:
Hypoxia for 24-60 h augmented PASMC proliferation (1.12±0.09 vs 0.71±0.05, P<0.05) and [Ca(2+) ]i [(214.8 ± 20.4) nmol/L vs (115.2±13.2) nmol/L, P<0.05] in a time-dependent manner with the maximum effect at 60 h. Perfusion of Ca(2+) -free Krebs solution containing nifedipine (5 µmol/L), cyclopiazonic acid (CPA, 10 µmol/L) in PASMCs caused a small transient increase of [Ca(2+) ]i with peak [Ca(2+) ]i (113.3±49.3) nmol/L.Chronic hypoxia (4% O2, 60 h) enhanced [Ca(2+) ]i level with peak value of (193.2±22.7) nmol/L (P<0.05) in PASMC.After restoration of extracellular Ca(2+) , CPA caused marked increase of [Ca(2+) ]i with peak value of (328.0 ±56.7) nmol/L.Chronic hypoxia strengthened CPA-induced increase of [Ca(2+) ]i with peak value of (526.0±33.7) nmol/L (P<0.05) in PASMCs.Either SKF96365 50 µmol/L or NiCl2 500 µmol/L distinctly attenuated CPA-induced enhancement of [Ca(2+) ]i, the peak value of which dropped from (526.0±33.7) nmol/L to (170.4±26.4) nmol/L (P<0.05) or (177.4±45.9) nmol/L (P<0.05) respectively.CONCLUSION:
Chronic hypoxia boosts the release of Ca(2+) from sarcoplasmic reticulum and promotes the activity of SOCC and SOCE, leading to [Ca(2+) ]i elevation and proliferation of rat PASMCs.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Artéria Pulmonar
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Bloqueadores dos Canais de Cálcio
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Nifedipino
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Canais de Cálcio
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Cálcio
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Hipóxia
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Músculo Liso Vascular
Limite:
Animals
Idioma:
Zh
Ano de publicação:
2016
Tipo de documento:
Article