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Cerivastatin inhibits fetal calf serunvinduced DNA synthesis in cultured rat mesangial cells
Author(s) -
HE JINSONG,
HORIKOSHI SATOSHI,
FUNABIKI KAZUHIKO,
SHIRATO ISAO,
TOMINO YASUHIKO
Publication year - 2002
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1046/j.1440-1797.2002.00077.x
Subject(s) - cerivastatin , dna synthesis , mesangial cell , mevalonate pathway , dna , biology , medicine , chemistry , endocrinology , biochemistry , biosynthesis , in vitro , cholesterol , enzyme , pravastatin
SUMMARY: Inhibition of mevalonate synthesis by several statins has been shown to suppress DNA synthesis in glomerular mesangial cells. In the present study, we investigated the effect of a new statin, cerivastatin, on fetal calf serum (FCS)‐induced DNA synthesis of cultured rat mesangial cells. Cultured rat mesangial cells were stimulated by 10% FCS in the presence or absence of cerivastatin and mevalonate. 5‐bromo‐2‐deoxyuridine (BrdU) incorporation was used to assess DNA synthesis. the present study showed that 10% FCS caused marked stimulation of DNA synthesis in the mesangial cells. Cerivastatin inhibited FCS‐stimulated BrdU incorporation in a dose‐dependent manner. IC 50 was approximately 1 umol/L. Exogenous mevalonate, farnesyl pyrophosphate and geranylgeranyl pyrophosphate significantly prevented the inhibitory effect of cerivastatin on DNA replication. It appears that cerivastatin, by inhibiting the synthesis of mevalonate, may suppress DNA synthesis in the mesangial cells.