del Carmen Puga Molina Lis, Verstraeten Sandra Viviana
Department of Biological Chemistry, IIMHNO (UBA) and IQUIFIB (UBA-CONICET), School of Pharmacy and Biochemistry, University of Buenos Aires, Argentina.
Biochim Biophys Acta. 2008 Oct;1778(10):2157-64. doi: 10.1016/j.bbamem.2008.04.013. Epub 2008 May 6.
Trivalent thallium (Tl(III)) is a highly toxic heavy metal through not completely understood mechanisms. Previously, we demonstrated that Tl(III) causes mitochondrial depolarization in PC12 cells leading to a decrease in cell viability. Given the role of the phospholipid cardiolipin (CL) in mitochondrial events, we evaluated in vitro the short- (2 min) and long- (60 min) time effects of Tl(III) (1-75 microM) on CL-containing membranes physical properties, and the consequences on cytochrome c binding to CL. After 2 min of incubation, Tl(III) significantly decreased liposome surface potential, lipid packing, and hydration of phosphatidylcholine:CL liposomes, while CL pK2 decreased from 9.8 to 8.2. The magnitude of these changes was even higher after 60 min of incubation. While no Tl(III) was found bound to membranes, Tl(I) was present in the samples. Accordingly, significant oxidative damage to both CL fatty acids and polar headgroup was observed. Cytochrome c binding to CL was decreased in Tl(III)-treated liposomes. The present results indicate that Tl(III) interaction with CL-containing membranes affected their physical properties, caused lipid oxidation and CL hydrolysis, and resulted in a decrease of cytochrome c binding. If occurring in vivo, these effects of Tl(III) could partially account for mitochondrial dysfunction in cells exposed to this metal.
三价铊（Tl(III)）是一种剧毒重金属，但其作用机制尚未完全明确。此前，我们证明了Tl(III)会导致PC12细胞线粒体去极化，进而降低细胞活力。鉴于磷脂心磷脂（CL）在线粒体事件中的作用，我们在体外评估了Tl(III)（1 - 75微摩尔）在短时间（2分钟）和长时间（60分钟）对含CL膜的物理性质的影响，以及对细胞色素c与CL结合的影响。孵育2分钟后，Tl(III)显著降低了磷脂酰胆碱：CL脂质体的脂质体表面电位、脂质堆积和水合作用，而CL的pK2从9.8降至8.2。孵育60分钟后，这些变化的幅度更大。虽然未发现有Tl(III)与膜结合，但样品中存在Tl(I)。相应地，观察到CL脂肪酸和极性头部均有明显的氧化损伤。在经Tl(III)处理的脂质体中，细胞色素c与CL的结合减少。目前的结果表明，Tl(III)与含CL膜的相互作用影响了其物理性质，导致脂质氧化和CL水解，并导致细胞色素c结合减少。如果在体内发生，Tl(III)的这些作用可能部分解释了暴露于这种金属的细胞中的线粒体功能障碍。
