Cellular protein synthesis and inhibition of cell division are independent of butyrate-induced histone hyperacetylation

Abstract

SODIUM BUTYRATE has many effects on mammalian cells—inducing the biosynthesis of new proteins^1–6, changing the relative synthetic rates of specific proteins^7–10, increasing various enzyme activities^7,9–13, inducing morphologic changes in cultured cells^9,12,14–19, and inhibiting DNA synthesis and cell division^14,15,20. The mechanism of these effects is not known. Sodium butyrate induces massive hyperacetylation of histone in cultured mammalian cells²¹ via inhibition of histone deacetylase^22–24: this hyperacetylation can be mimicked to varying degrees by other salts of short-chain fatty acids²². As histones interact so intimately with DNA, and as the change in extent of histone acetylation is so great, we sought to determine whether the changes in histone modification are involved in causing the changes in synthesis of specific proteins or the cessation of DNA synthesis and cell division. In hepatoma tissue culture (HTC) cells, the increased amount of histone acetylation is maximal 6–12 h after administration of sodium butyrate²², and we have used two-dimensional gel techniques²⁵ to establish whether different proteins are made during this period. Our results suggest that cellular protein synthesis and inhibition of cell division are independent of butyrate-induced hyperacetylation.