Suppression of fibroblast growth factor-2 expression: possible mechanism underlying methylmercury-induced inhibition of the repair of wounded monolayers of cultured human brain microvascular endothelial cells.
Vascular toxicity is an important feature of the neuropathy induced by methylmercury. Methylmercury does not cause nonspecific cell damage, but rather retards the repair of wounded monolayers of cultured human brain microvascular endothelial cells by inhibiting their proliferation. Since vascular endothelial cell proliferation during the repair process strongly depends on the fibroblast growth factor-2 (FGF-2) system, we investigated the effects of methylmercury on the expression of FGF-2 and related proteins (i.e., FGF receptor 1 and perlecan) in cultured human brain microvascular endothelial cells. Of the mRNAs examined, FGF-2 mRNA expression was significantly lowered by methylmercury in not only wounded monolayers but also dense and sparse cultures of endothelial cells; a lower expression of FGF-2 protein in the cells was confirmed. In addition, exogenous FGF-2 partially abrogated the proliferation-inhibitory effect of methylmercury. The results of this study suggest that suppression of FGF-2 expression is one of the mechanisms underlying the inhibitory effect of methylmercury in damaged endothelial cell monolayers. The FGF-2 system may be one of the important biological systems behind the vascular toxicity of methylmercury.
Hirooka
Takashi
T
Fujiwara
Yasuyuki
Y
Inoue
Shoko
S
Shinkai
Yasuhiro
Y
Yamamoto
Chika
C
Satoh
Masahiko
M
Yasutake
Akira
A
Eto
Komyo
K
Kaji
Toshiyuki
T
D001921:Brain / Q000098:blood supply*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003864:Depression, Chemical; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D008767:Methylmercury Compounds / Q000633:toxicity*; D008833:Microcirculation; D012333:RNA, Messenger / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects*
D008767:Methylmercury Compounds; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2