Modulation of cholesterol 7α-hydroxylase activity by nonspecific lipid transfer protein in human liver — possibly altered regulation of its cytosolic level in patients with gallstones

Abstract

Nonspecific lipid transfer protein (nsLTP) partially purified from human liver stimulated human microsomal cholesterol 7α-hydroxylase activity. Addition of the nsLTP preparation to the reaction mixture enhanced the activity two-fold. Treatment of the nsLTP preparation with anti-rat nsLTP antiserum, which cross-reacts with human nsLTP, reduced the 7α-hydroxylase-stimulating ability. These observations suggested that nsLTP plays a role in regulating the 7α-hydroxylase activity in the human liver. 7α-Hydroxylase activity in eight patients with cholesterol gallstones (4.7 ± 1.6 pmol/min per mg microsomal protein) was significantly lower than that in five controls (7.9 ± 3.4) ( P < 0.05). The amount of nsLTP in the cytosolic fraction (105000 × g supernatant) of human liver was determined by dot-blotting immunoquantitation with the antiserum. The cytosolic level of nsLTP in the liver of the patients (716 ± 239 cpm/3 μg protein) was higher than that in the controls (438 ± 184) although the difference between the two groups was not statistically significant. This suggested that control of the cytosolic level may be affected in patients with cholesterol gallstones.