著者
Musubu Takahashi Ayaka Kubota Tomoya Fujie Yasuhiro Shinkai Yoshito Kumagai Tsuyoshi Nakano Takato Hara Chika Yamamoto Toshiyuki Kaji
出版者
The Pharmaceutical Society of Japan
雑誌
BPB Reports (ISSN:2434432X)
巻号頁・発行日
vol.4, no.6, pp.175-181, 2021 (Released:2021-11-12)
参考文献数
27
被引用文献数
2

Fibroblast growth factor-2 (FGF-2) regulates several vascular endothelial cell functions, including proliferation. It has been suggested that the regulation may be modulated by reactive sulfur species (RSS), which are hydrogen sulfide and biomolecules containing persulfide/polysulfide groups. Since RSS promote vascular endothelial cell proliferation, we hypothesized that FGF-2 regulates the levels of RSS-producing enzymes in the cells. Bovine aortic endothelial cells were cultured and treated with FGF-2, and intracellular RSS levels were determined. The expression of RSS-producing enzymes, cystathionine γ-lyase (CSE), cystathionine β-synthase, 3-mercaptopyruvate sulfurtransferase, and cysteinyl-tRNA synthetase 2, was evaluated, and the intracellular signaling pathway that mediates FGF-2 regulation of RSS accumulation was investigated. We revealed that FGF-2 upregulates the expression of RSS by selectively inducing CSE via the ERK1/2 signaling pathway in vascular endothelial cells. The effect of FGF-2 on the function of vascular endothelial cells may be modulated by intracellular RSS, especially higher-molecular-mass RSS such as protein persulfide, the levels of which are increased by the growth factor.
著者
Musubu Takahashi Ruri Iwai Ryoko Takasawa Tsuyoshi Nakano Tomoya Fujie Takato Hara Yasushi Hara Chika Yamamoto Toshiyuki Kaji
出版者
The Japanese Society of Toxicology
雑誌
The Journal of Toxicological Sciences (ISSN:03881350)
巻号頁・発行日
vol.46, no.7, pp.341-344, 2021 (Released:2021-07-01)
参考文献数
11
被引用文献数
3

Reactive sulfur species (RSS) include biological persulfide molecules that protect cells against oxidative stress and heavy metal toxicity. Vascular endothelial cells regulate blood coagulation and fibrinolytic activity, and prevent vascular disorders such as atherosclerosis. We hypothesized that RSS protect vascular endothelial cells not only from nonspecific cell damage but also from specific functional damage through regulation of specific cell functions. In the present study, cultured bovine aortic endothelial cells were treated with sodium trisulfide, a sulfane sulfur donor, and both [3H]thymidine incorporation and effects on cell cycle were analyzed. These results suggest that RSS stimulate vascular endothelial cell proliferation. RSS may reduce the functional cytotoxicity of antiproliferative agents.