Inhibition of the cystathionine-gamma-lyase/hydrogen sulfide pathway in rat vascular smooth muscle cells by cobalt-60 gamma radiation.
BACKGROUND
Radiation is a promising treatment for in stent restenosis and restenosis following percutaneous transluminal coronary angioplasty, which has troubled interventional cardiologists for a long time. It inhibits neointima hyperplasia, vascular remodeling, and increases the mean luminal diameter. The mechanism of intracoronary brachytherapy for restenosis is not well understood. Endogenous gaseous transmitters including nitric oxide and carbon monoxide are closely related to restenosis. Hydrogen sulfide, a new endogenous gaseous transmitter, is able to inhibit the proliferation of vascular smooth muscle cells and vascular remodeling. This study aimed to clarify the effect of radiation on cystathionine-gamma-lyase/hydrogen sulfide pathway in rat smooth muscle cells.


METHODS
We studied the effect of radiation on the cystathionine-gamma-lyase/hydrogen sulfide pathway. Rat vascular smooth muscle cells were radiated with (60)Co gamma at doses of 14 Gy and 25 Gy respectively. Then the mRNA level of cystathionine-gamma-lyase was studied by quantitative reverse-transcription competitive polymerase chain reaction. Hydrogen sulfide concentration in culture medium was determined by methylene blue spectrophotometry. Cystathionine-gamma-lyase activity in vascular smooth muscle cells was also studied.


RESULTS
(60)Co gamma radiation at a dose of 1 Gy did not affect the cystathionine-gamma-lyase/hydrogen sulfide pathway significantly. However, (60)Co gamma radiation at doses of 14 Gy and 25 Gy decreased the hydrogen sulfide synthesis by 21.9% (P<0.05) and 26.8% (P<0.01) respectively. At the same time, they decreased the cystathionine-gamma-lyase activity by 15.1% (P<0.05) and 20.5% (P<0.01) respectively, and cystathionine-gamma-lyase mRNA expression by 29.3% (P<0.01) and 38.2% (P<0.01) respectively.


CONCLUSIONS
Appropriate (60)Co gamma radiation inhibits the H(2)S synthesis by inhibiting the gene expression of cystathionine-gamma-lyase and the cystathionine-gamma-lyase activity.
Zhong
Guang-zhen
GZ
Department of Cardiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China. zhongguangzhen@hotmail.com
Yang
Xin-chun
XC
Jia
Li-ping
LP
Chen
Feng-rong
FR
Cui
Ming
M
D000818:Animals; D002478:Cells, Cultured; D003037:Cobalt Radioisotopes; D003542:Cystathionine gamma-Lyase / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D005720:Gamma Rays; D006862:Hydrogen Sulfide / Q000378:metabolism*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects
D003037:Cobalt Radioisotopes; D003542:Cystathionine gamma-Lyase; D006862:Hydrogen Sulfide