外源性磷脂酶、花生四烯酸和1-油酰基-2-乙酰基-sn-甘油对分离的大鼠肝细胞生酮作用的影响。

Effects of exogenous phospholipase enzymes, arachidonic acid and 1-oleoyl-2-acetyl-sn-glycerol on ketogenesis in isolated rat hepatocytes.

作者信息

Chihara M, Nomura T, Tachibana M, Nomura H, Nomura Y, Hagino Y

机构信息

Department of Pharmacology, Fujita-Gakuen Health University School of Medicine, Aichi, Japan.

出版信息

Biochim Biophys Acta. 1989 Jun 15;1012(1):5-9. doi: 10.1016/0167-4889(89)90003-7.

DOI:10.1016/0167-4889(89)90003-7

PMID:2499356

Abstract

Studies were conducted to see whether exogenous phospholipase C from Clostridium perfringens, phospholipase A2 from Crotalus adamanteus venom, arachidonic acid and 1-oleoyl-2-acetyl-sn-glycerol (OAG) mimic the anti-ketogenic action of vasopressin in isolated rat hepatocytes. Exogenous phospholipase C inhibited ketogenesis in the presence of 0.5 mM oleate. Experiments employing [1-14C]oleate, however, indicated that the mechanism involved in the anti-ketogenic action of exogenous phospholipase C is distinct from that of vasopressin. The decreased rate of the production of acid-soluble products from [1-14C]oleate in response to vasopressin could be explained by the sum of the increased rates of 14CO2 formation and [1-14C]oleate esterification. By contrast, exogenous phospholipase C suppressed not only the formation of acid-soluble products but also 14CO2 production and [1-14C]oleate esterification. Indeed, phospholipase C greatly inhibited [1-14C]oleate uptake into hepatocytes. It is suggested that the alteration of the architecture of plasma membrane by exogenous phospholipase C may lead to the disturbance of oleate uptake and consequent general suppression of oleate metabolism. Exogenous phospholipase A2, arachidonic acid and OAG increased ketogenesis regardless of the presence of oleate. The ketogenic effects may be attributed to the supply of fatty acids by these agents to hepatocytes.

摘要

开展了多项研究，以观察来自产气荚膜梭菌的外源性磷脂酶C、矛头蝮蛇毒中的磷脂酶A2、花生四烯酸和1-油酰基-2-乙酰基-sn-甘油（OAG）是否能模拟血管加压素在分离的大鼠肝细胞中的抗生酮作用。在外源性磷脂酶C存在0.5 mM油酸的情况下，其抑制了生酮作用。然而，采用[1-14C]油酸的实验表明，外源性磷脂酶C的抗生酮作用机制与血管加压素不同。血管加压素作用下，[1-14C]油酸产生酸溶性产物的速率降低，这可以通过14CO2生成速率和[1-14C]油酸酯化速率的增加之和来解释。相比之下，外源性磷脂酶C不仅抑制了酸溶性产物的形成，还抑制了14CO2的产生和[1-14C]油酸的酯化。事实上，磷脂酶C极大地抑制了[1-14C]油酸进入肝细胞。提示外源性磷脂酶C对质膜结构的改变可能导致油酸摄取紊乱，进而全面抑制油酸代谢。无论是否存在油酸，外源性磷脂酶A2、花生四烯酸和OAG均增加了生酮作用。这些生酮作用可能归因于这些物质向肝细胞提供了脂肪酸。