Open AccessNotoginsenoside Rb1 inhibits activation of ERK and p38 MAPK pathways induced by hypoxia and hypercapnia
Author(s) -
Xiaoxiao Qiu,
MingHua Zheng,
Dong Keun Song,
Linli Huang,
Liyang Tang,
Ying Lei,
Wan-Tie Wang
Publication year - 2016
Publication title -
experimental and therapeutic medicine
Language(s) - English
Resource type - Journals
eISSN - 1792-1015
pISSN - 1792-0981
DOI - 10.3892/etm.2016.3217
Subject(s) - hypercapnia , hypoxia (environmental) , mapk/erk pathway , p38 mitogen activated protein kinases , molecular medicine , microbiology and biotechnology , apoptosis , cell cycle , oncogene , chemistry , signal transduction , biology , medicine , respiratory system , biochemistry , organic chemistry , oxygen
The aim of the present study was to investigate the effect of notoginsenoside Rb1 (Rb1) on the ERK and p38 MAPK pathways in primary cultured pulmonary arterial smooth muscle cells (PASMCs) exposed to hypoxia and hypercapnia, in order to elucidate the mechanism underlying the effect of Rb1 on hypoxia and hypercapnia-induced pulmonary vasoconstriction (HHPV). PASMCs were isolated from Sprague-Dawley rats. The cells were divided into five groups: Normal (N), hypoxia and hypercapnia (H), Rb L , Rb M and Rb H groups. N group cells were cultured under 5% CO 2 and 21% O 2 . H, Rb L , Rb M and Rb H groups were cultured under 6% CO 2 and 1% O 2 . Prior to the hypoxia and hypercapnia exposure, Rb L , Rb M and Rb H groups were treated with 8, 40 and 100 mg/ml Rb1 for 30 min, respectively. Phosphorylated extracellular signal-regulated kinase (P-ERK) and P-p38 protein, and ERK1/2 and p38 mRNA expression levels were detected using western blot and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analyses, respectively. The correlations between P-ERK protein and ERK1/2 mRNA, and between P-p38 protein and p38 mRNA were evaluated. Results of western blot and RT-PCR showed hypoxia and hypercapnia increased P-ERK and P-p38 protein, and ERK1/2 mRNA, respectively (P<0.05). Rb1 suppressed the increased P-ERK and P-p38 protein, and ERK1/2 and p38 mRNA by hypoxia and hypercapnia (P<0.05). P-ERK protein was positively correlated with ERK1 (r=0.5, P<0.01) and ERK2 mRNA (r=0.977, P<0.01). P-p38 protein was positively correlated with p38 mRNA (r=0.884, P<0.01). Thus, the present results indicate that Rb1 may ameliorate HHPV by suppressing ERK and p38 pathways. The study provides an experimental basis for investigating the clinical use of Rb1 in the management of HHPV-related disorders.