Synergistic stimulation of pregnenolone synthesis in rat adrenal mitochondria by n-hexane and cardiolipin.
Synergistic stimulation of pregnenolone synthesis in rat adrenal mitochondria by n-hexane and cardiolipin.
复制标题
正己烷和心磷脂对大鼠肾上腺线粒体孕烯醇酮合成的协同刺激。
DOI：
10.1016/0003-9861(88)90508-5
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发表时间：
1988
影响因子：
3.9
通讯作者：
Jefcoate,CR
中科院分区：
文献类型：
--
作者：
McNamara,BC;Jefcoate,CR
正己烷和心磷脂分别刺激分离的大鼠肾上腺线粒体产生孕烯醇酮。促肾上腺皮质激素(ACTH)刺激后，线粒体胆固醇代谢呈现一个持续2分钟的快速阶段，随后代谢速度减慢10倍。用地塞米松或放线菌酮(CX)抑制ACTH可消除这一快相。当正己烷的浓度接近水溶极限的80%(~0.08 mM)时，选择性地刺激代谢的慢相，而心磷脂(100μm)只刺激快相。其他烷烃和醚是有效的。正己烷的作用依赖于线粒体的完整性，表现在低渗休克线粒体的作用减弱(外膜破坏)和超声处理的线粒体无效(两膜破坏)。正己烷明显促进外膜胆固醇向内膜的转移。心磷脂的刺激被破坏的线粒体保留，并可能涉及增加对内膜胆固醇的可利用性。当这些药物加在一起时，对胆固醇新陈代谢产生的不仅仅是相加的影响。用正己烷预孵育并不增加反应性胆固醇，这表明增强的胆固醇转运只与内膜胆固醇的新陈代谢相一致。烷烃摄取到线粒体膜可能会影响促进外膜到内膜胆固醇转移的结构变化，但作为P-450scc的还原剂的异柠檬酸的有效性排除了主要变化。在组合中，正己烷和心磷脂复制了对ACTH敏感的固醇调节肽对线粒体的影响[R.C.Pedersen和A.C.Brownie(1983)过程。娜塔莉。阿卡德。SCI。USA80,1882-1886]，表明作用于肾上腺线粒体的多肽可能分解成两个类似的成分。
n-Hexane and cardiolipin each stimulate pregnenolone production by isolated rat adrenal mitochondria. Following corticotropin (ACTH) stimulation, mitochondrial cholesterol metabolism exhibits a fast phase lasting 2 min, followed by a 10-fold slower metabolism. ACTH suppression by dexamethazone or cycloheximide (CX) treatment removes this fast phase.n-Hexane, at concentrations approaching 80% of the aqueous solubility limit (~0.08 mm), selectively stimulates the slow phase of metabolism, while cardiolipin (100 μm) stimulates only the fast phase. Other alkanes and ethers are effective. The effect ofn-hexane is dependent on mitochondrial integrity, as evidenced by decreased effects in hypoosmotically shocked mitochondria (outer membrane disrupted) and ineffectiveness in sonicated mitochondria (both membranes disrupted).n-Hexane apparently enhances the transfer of outer membrane cholesterol to inner membraneP-450scc. Stimulation by cardiolipin is retained by disrupted mitochondria and may involve enhanced availability ofP-450sccto inner membrane cholesterol. When added together, these agents produce more than additive effects on cholesterol metabolism. Preincubation withn-hexane did not increase reactive cholesterol, suggesting that enhanced cholesterol transport occurs only in concert with metabolism of inner membrane cholesterol. Uptake of alkanes into mitochondrial membranes may effect structural changes that facilitate outer to inner membrane cholesterol transfer, but major changes are excluded by the effectiveness of isocitrate as a reductant forP-450scc. In combination,n-hexane and cardiolipin reproduce the effect of the ACTH-sensitive sterol regulatory peptide on mitochondria [R. C. Pedersen and A. C. Brownie (1983)Proc. Natl. Acad. Sci. USA80, 1882–1886], suggesting that peptide action on adrenal mitochondria may resolve into two analogous components.