Open AccessSodium butyrate is a potent modulator of smooth muscle cell proliferation and gene expression
Author(s) -
Feng P.,
Ge L.,
Akyhani N.,
Liau G.
Publication year - 1996
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1046/j.1365-2184.1996.00998.x
Subject(s) - sodium butyrate , butyrate , dna synthesis , cell growth , cell cycle , microbiology and biotechnology , biology , intracellular , biochemistry , cell , dna , chemistry , gene , fermentation
Sodium butyrate is a small, naturally occurring molecule with demonstrated activity on cell growth and differentiation. However, its effect on smooth muscle cells had not been examined. We have found that sodium butyrate and its more stable in vivo analogue tributyrin are potent DNA synthesis and cell proliferation inhibitors. The inhibitory activity of sodium butyrate was not mediated by an elevation of endogenous cAMP levels, a known pathway involved in SMC growth‐arrest and maintenance of the contractile phenotype. Consistent with the concept that its activity is mediated by a cAMP‐independent pathway, butyrate was able to augment the maximum DNA synthesis inhibitory effect of various agents that elevated intracellular cAMP levels. Additionally, butyrate present for just the initial 8 h or present as late as 16 h after serum addition was able to inhibit DNA synthesis. By contrast, the cAMP analogue, 8Br‐cAMP had to be present throughout the entire G 0 to S phase of the cell cycle to effectively inhibit DNA synthesis. These results indicated that sodium butyrate inhibited SMC growth through a cAMP‐independent mechanism. We also found that sodium butyrate was unable to abrogate the expression of the serum‐inducible genes c‐ fos , c‐ myc , Ki‐Ras and PS4, but was able to directly stimulate the expression of PS4 and thrombospondin. These results indicate that a number of important early G 1 events initiated by serum growth factors are unaltered by sodium butyrate and that this compound is able to directly stimulate the expression of certain genes normally associated with SMC proliferation.