The possible role of Ca2+ on the activation of microsomal triglyceride transfer protein in rat hepatocytes.

Microsomal triglyceride (TG) transfer protein (MTP) is involved in the secretion of TG-rich very low-density lipoprotein (VLDL), a process which leads to the generation of hypertriglyceridemia and atherosclerosis. We investigated the possible role of Ca(2+) on MTP activity in hepatocytes. Exogenous CaCl(2) and calmodulin increased MTP activity dose-dependently, and calcium ionophore A23187 (A23187) also increased total Ca(2+) level and MTP activity in hepatocytes. Moreover, MTP activity increased by CaCl(2) or A23187 was abrogated in the presence of EDTA, a Ca(2+) chelator. MTP activity was increased by the simultaneous addition of CaCl(2) and calmodulin. However, this increase was inhibited by N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), a Ca(2+) antagonist. A23187 increased the release of TG and cholesterol from hepatocytes, and these were inhibited by EDTA. A23187 also increased the ratio of TG to HDL-cholesterol in hepatocytes culture medium, which indicates the release of TG is higher than that of HDL-cholesterol from hepatocytes. Thus, our findings demonstrate that hepatocellular Ca(2+) contributes directly or indirectly to MTP activation. In conclusion, the inhibition of MTP activity via the suppression of hepatocellular Ca(2+) may result in the inhibition of hypertriglyceridemia.