Salerno C, Capuozzo E, Crifò C, Siems W
Department of Gynecology, Perinatology and Child Health, Sapienza University of Rome, via dei Sardi 58, 00185 Rome, Italy.
Biochim Biophys Acta. 2007 Sep;1772(9):1052-6. doi: 10.1016/j.bbadis.2007.05.008. Epub 2007 Jun 6.
It has been found that beta-carotene cleavage products (CarCP), besides having mutagenic and toxic effects on mitochondria due to their prooxidative properties, also initiate spontaneous apoptosis of human neutrophils. Therefore, it was expected that antioxidants such as alpha-tocopherol would inhibit the stimulation of apoptosis and caspase-3 activity by CarCP. However, we found that alpha-tocopherol increases caspase-3 up-regulation and stimulation of apoptosis of human neutrophils by CarCP. Ascorbic acid does not alter this caspase-3 up-regulating and proapoptotic effect exerted by alpha-tocopherol. Both alpha-tocopherol and ascorbic acid, in the absence of CarCP, decrease intracellular caspase-3 activity and spontaneous apoptosis of neutrophils. Uric acid alone or in combination with CarCP does not exert apparent effects on caspase-3 activity and apoptosis. Up-regulating effect of alpha-tocopherol is not observed in the presence of retinol that markedly stimulates apoptosis by itself, whereas increase of caspase-3 activity is induced by concomitant addition of alpha-tocopherol and beta-ionone, a cyclohexenyl degradation product of beta-carotene with shorter aliphatic chain.
已发现，β-胡萝卜素裂解产物（CarCP）除因其促氧化特性对线粒体具有诱变和毒性作用外，还会引发人类中性粒细胞的自发凋亡。因此，预计抗氧化剂如α-生育酚会抑制CarCP对凋亡和半胱天冬酶-3活性的刺激。然而，我们发现α-生育酚会增加CarCP对人类中性粒细胞凋亡的半胱天冬酶-3上调和刺激作用。抗坏血酸不会改变α-生育酚所发挥的这种半胱天冬酶-3上调和促凋亡作用。在不存在CarCP的情况下，α-生育酚和抗坏血酸都会降低细胞内半胱天冬酶-3活性和中性粒细胞的自发凋亡。单独的尿酸或与CarCP联合使用对半胱天冬酶-3活性和凋亡均无明显影响。在视黄醇存在的情况下未观察到α-生育酚的上调作用，视黄醇自身会显著刺激凋亡，而同时添加α-生育酚和β-紫罗兰酮（β-胡萝卜素具有较短脂肪链的环己烯基降解产物）会诱导半胱天冬酶-3活性增加。
