Yahuaca P, Amaya A, Rojkind M, Mourelle M
Lab Invest. 1985 Nov;53(5):541-5.
The activities of Na+,K+-, and Ca2+-ATPases were determined in plasma membranes obtained from livers of rats treated acutely and chronically with CCl4. Twenty-four hours after a single oral dose of CCl4 the ATPases decreased below 50% of control values. The activity of Ca2+-ATPase returned to normal after 4 days, and Na+,K+-ATPase activity returned to normal values after 12 days. One week after initiation of the chronic intraperitoneal treatment with CCl4, the Na,K+-ATPase decreased to 40% of control values and continued to decrease further until reaching values below 1%. Ca2+-ATPase followed a pattern similar to that obtained with Na+,K+-ATPase, except that the decrease was not as severe. Colchicine treatment prevented the modifications in ATPases when given simultaneously with CCl4 and reverted the alterations in ATPase activities of the CCl4-cirrhotic animals. Because ATPases are known to be modulated by the lipid composition of the membrane, we also determined the cholesterol to phospholipid ratio in all the isolated membranes. The ratios were increased in membranes with low ATPase activity due to an increase in the total concentration of cholesterol. Plasma membranes of cirrhotic rats treated with colchicine showed a low concentration of cholesterol, a decreased cholesterol to phospholipid ratio, and Na+,K+-ATPase activity was almost normal. When plasma membranes of cirrhotic rats were fused with phosphatidyl serine-containing liposomes, the cholesterol to phospholipid ratio decreased and the ATPase activity increased. The ATPase activity of normal plasma membranes decreased below 20% of control values when enriched with cholesterol. Our results suggest that the decrease in the plasma membrane Na+,K+-ATPase activity of the cirrhotic rat is due in part to an increase in its cholesterol concentration and in the cholesterol to phospholipid ratio.
在急性和慢性给予四氯化碳（CCl4）处理的大鼠肝脏所获得的质膜中，测定了钠钾ATP酶（Na +,K + -ATPase）和钙ATP酶（Ca2 + -ATPase）的活性。单次口服CCl4 24小时后，这些ATP酶活性降至对照值的50%以下。Ca2 + -ATP酶活性在4天后恢复正常，而Na +,K + -ATP酶活性在12天后恢复正常。在用CCl4进行慢性腹腔注射处理1周后，钠钾ATP酶降至对照值的40%，并继续进一步下降，直至降至1%以下。Ca2 + -ATP酶呈现出与Na +,K + -ATP酶相似的模式，只是下降程度没那么严重。秋水仙碱处理在与CCl4同时给予时可防止ATP酶的改变，并使CCl4诱导肝硬化动物的ATP酶活性改变恢复正常。由于已知ATP酶受膜脂质组成的调节，我们还测定了所有分离膜中的胆固醇与磷脂比率。由于胆固醇总浓度增加，ATP酶活性低的膜中该比率升高。用秋水仙碱处理的肝硬化大鼠的质膜显示胆固醇浓度低、胆固醇与磷脂比率降低，且Na +,K + -ATP酶活性几乎正常。当将肝硬化大鼠的质膜与含磷脂酰丝氨酸的脂质体融合时，胆固醇与磷脂比率降低，ATP酶活性增加。当用胆固醇富集时，正常质膜的ATP酶活性降至对照值的20%以下。我们的结果表明，肝硬化大鼠质膜中Na +,K + -ATP酶活性的降低部分归因于其胆固醇浓度及胆固醇与磷脂比率的增加。
