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莫里斯7777肝癌中线粒体功能和脂质组成的改变。

Alteration of mitochondrial function and lipid composition in Morris 7777 hepatoma.

作者信息

Morton R, Cunningham C, Jester R, Waite M, Miller N, Morris H P

出版信息

Cancer Res. 1976 Sep;36(9 pt.1):3246-54.

PMID:184946
Abstract

Mitonchondria isolated from the Morris hepatoma 7777 demonstrated a markedly different phospholipid composition from those of control mitochondria, both with respect to the amounts of the various types present and the fatty acid composition. The level of polyunsaturated fatty acids in the mitochondrial phospholipids was lowered, wheras there was an increase in the level of monounsaturated fatty acids. Moreover, the usual distribution of saturated fatty acids at position 1 and polyunsaturated fatty acids at position 2 does not exist in hepatoma phospholipids; a high percentage of monounsaturated fatty acids was found at both positions. The cardiolipin content was lower in hepatoma mitochondria (3.7%) than in livers of animals with hepatomas (5.2%). There was, however, some compensation in the amount of acidic phospholipids in these mitochondria due to an increase in phosphatidylserine (4.9% versus 1.3%). The force-area curves of the hepatoma phospholipids spread on a monomolecular film demonstrated a smaller area per molecule than those from liver mitochondria. The zeta potential of liposomes of the hepatoma phospholipids (-45) was less than those of control mitochondria (-81), as determined by microelectrophoresis. The calcium-stimulated phospholipase A activity of the hepatoma mitochondria appeared to be more readily expressed than the same activity in liver organelles. The maximal activity was lower, however, than that noted in liver mitochondria. Furthermore, by following the incorporation of [3H]ethanolamine into mitochondria phospholipids, it was established that the conversion of glycerophosphorylethanolamine to glycerophosphorylcholine was increased in the hepatoma. These observations suggest dramatic changes in phospholipid metabolism in the hepatoma, at the level of both the endoplasmic reticulum and the mitochondrion. Accompanying the changes in phospholipid compositon and metabolism were alterations in mitochondrial energy-linked processes. The hepatoma mitochondria demonstrated lower respiratory control ratios even when isolated in an isotonic solution containing 1mM ethylenediaminetetraacetate and bovine serum albumin (0.5 mg/ml). This was due to increased state 4 respiration.

摘要

从莫里斯肝癌7777中分离出的线粒体,其磷脂组成与对照线粒体相比有显著差异,无论是各种类型磷脂的含量还是脂肪酸组成。线粒体磷脂中多不饱和脂肪酸的水平降低,而单不饱和脂肪酸的水平升高。此外,肝癌磷脂中不存在饱和脂肪酸在1位、多不饱和脂肪酸在2位的通常分布;在这两个位置都发现了高比例的单不饱和脂肪酸。肝癌线粒体中的心磷脂含量(3.7%)低于患肝癌动物肝脏中的含量(5.2%)。然而,由于磷脂酰丝氨酸增加(4.9%对1.3%),这些线粒体中酸性磷脂的量有一定补偿。铺展在单分子膜上的肝癌磷脂的力-面积曲线显示,每个分子的面积比肝脏线粒体的小。通过微电泳测定,肝癌磷脂脂质体的ζ电位(-45)低于对照线粒体的ζ电位(-81)。肝癌线粒体中钙刺激的磷脂酶A活性似乎比肝脏细胞器中的相同活性更容易表达。然而,最大活性低于肝脏线粒体中的活性。此外,通过追踪[3H]乙醇胺掺入线粒体磷脂的过程,确定肝癌中甘油磷酸乙醇胺向甘油磷酸胆碱的转化增加。这些观察结果表明,肝癌在内质网和线粒体水平上磷脂代谢发生了显著变化。伴随着磷脂组成和代谢的变化,线粒体能量相关过程也发生了改变。即使在含有1mM乙二胺四乙酸和牛血清白蛋白(0.5mg/ml)的等渗溶液中分离,肝癌线粒体的呼吸控制率也较低。这是由于状态4呼吸增加所致。

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