Induction by short‐chain fatty acids of alkaline phosphatase activity in cultured mammalian cells

Abstract

Short‐chain fatty acids, such as propionic, n‐butyric, n‐valeric, isovaleric, n‐caproic, and n‐caprylic acids, induce alkaline phosphatase activity in cultured mammalian cells. Long‐chain fatty acids have no similar effects. With B‐6 cells (mouse × Chinese hamster cell hybrids), n‐butyrate at 2 to 5 mM exhibits the greatest activity. Induction begins exponentially about 24 hours after addition of the fatty acid and continues over 48 hours. Studies on the inducing activity‐structure relationship revealed the necessity of a carboxyl and an ethyl or longer alkyl group. n‐Butyrate shows a marked synergistic action of induction when added along with other types of inducers: adenosine 3′:5′‐cyclic monophosphate (cAMP) or 5‐bromodeoxyuridine (BrdU). Treatment of other cell lines with either n‐butyrate, cAMP, or BrdU revealed a cell‐type specific response pattern of alkaline phosphatase. The biological significance of this effect of short‐chain fatty acids is discussed. 1 This study was presented in part at the 45th Annual Meeting of the Japanese Biochemical Society, Tokyo, October, 1972. After submission of this manuscript, the authors noticed a similar study on alkaline phosphatase induction by n‐butyrate, reported by M. J. Griffin et al. ('74) in Arch. Biochem. Biophys., 164: 619–623.