Acta Pharmacologica Sinica 2006 December; 27 (12): 1561-1566; doi: 10.1111/j.1745-7245.2006.00425.x

 
Original Article
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Interaction between hydrogen sulfide/cystathionine γ-lyase and carbon monoxide/heme oxygenase pathways in aortic smooth muscle cells
 

Hong-fang JIN2, Jun-bao DU2,4, Xiao-hui LI2, Yan-fei WANG2, Yin-fang LIANG2, Chao-shu TANG3

2Department of Pediatrics, Peking University First Hospital, Beijing 100034, China; 3Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China

 

Aim: To investigate the interaction between hydrogen sulfide (H2S)/cystathionine γ-lyase (CSE) and carbon monoxide (CO)/heme oxygenase (HO) pathways in aortic smooth muscle cells (ASMC).

 

Methods: The ASMCs were divided into the following groups: (1) the control group; (2) the zinc protoporphyrin (ZnPP) 20 µmol/L group; (3) the propargylglycine (PPG) 2 mmol/L, 4 mmol/L and 10 mmol/L groups; and (4) the sodium hydrosulfide (NaHS) 1×10-5 mol/L, 1×10-4 mol/L and 1×10-3 mol/L groups. Each of the groups was further divided into 6 h, 12 h, 18 h and 24 h subgroups. The CO level, represented by carboxyhemoglobin (HbCO) content was measured using a spectrophotometric method and H2S content was detected by a sensitive electrode method. CSE and HO-1 expressions were detected by Western blotting.

 

Results: The H2S content in the medium and CSE expression by ASMC were markedly increased by ZnPP compared with the control group. HbCO content in the medium and HO-1 expression by the ASMC started strengthening following 24 h treatment with PPG at 2 mmol/L, but were further strengthened following 18 h and 24 h treatment with PPG at 4 mmol/L compared with the controls (P<0.01). PPG at 10 mmol/L increased the HbCO level in the medium following 18 h treatment and increased HO-1 expression by the ASMC following 12 h treatment. Moreover, NaHS at 1×10-5 mol/L and 1×10-4 mol/L decreased the HbCO level in the medium and HO-1 expression by the ASMC after 6 h and 12 h treatment, while NaHS at 1×10-3 mol/L decreased them at all time points of the treatments.


Conclusion:
The results suggested that endogenous CO/HO and H2S/CSE pathways inhibited each other in ASMC under physiological conditions.

 

Keywords: hydrogen sulfide; cystathionine γ-lyase; carbon monoxide; heme oxygenase

 
1 Project supported by the National Natural Science Fundation for Distinguished Young Scholars (No 30425010), National Natural Science Foundation of China (No 30571971) and the State Major Basic Key Research Program (No 2006CB503807).

4 Correspondence to Prof Jun-bao DU.
Phn 86-10-6655-1122, ext 3238.
Fax 86-10-6613-4261.
E-mailjunbaodu@ht.rol.cn.net
Received 2006-04-26       Accepted 2006-06-13

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