Department of Cytology and Histology, Okayama University Graduate School, Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Biochem Biophys Res Commun. 2011 Aug 19;412(1):61-7. doi: 10.1016/j.bbrc.2011.07.039. Epub 2011 Jul 21.
Cardiovascular risks are frequently accompanied by high serum fatty acid levels. Although recent studies have shown that fatty acids affect mitochondrial function and induce cell apoptosis, L-carnitine is essential for the uptake of fatty acids by mitochondria, and may attenuate the mitochondrial dysfunction and apoptosis of cardiocytes. This study aimed to elucidate the activity of L-carnitine in the prevention on fatty acid-induced mitochondrial membrane permeability transition and cytochrome c release using isolated cardiac mitochondria from rats. Palmitoyl-CoA-induced mitochondrial respiration that was observed with L-carnitine was inhibited with oligomycin. The palmitoyl-CoA-induced mitochondrial membrane depolarization and swelling were greatly inhibited by the presence of L-carnitine. In ultrastructural observations, terminally swollen and ruptured mitochondria with little or no distinguishable cristae structures were induced by treatment with palmitoyl-CoA. However, the severe morphological damage in cardiac mitochondria was dramatically inhibited by pretreatment with L-carnitine. Treatment with L-carnitine also attenuated 4-hydroxy-L-phenylglycine- and rotenone-induced mitochondrial swelling even when the L-carnitine could not protect against the decrease in oxygen consumption associated with these inhibitors. Furthermore, L-carnitine completely inhibited palmitoyl-CoA-induced cytochrome c release. We concluded that L-carnitine is essential for cardiac mitochondria to attenuate the membrane permeability transition, and to maintain the ultrastructure and membrane stabilization, in the presence of high fatty acid β-oxidation. Consequently, the cells may be protected against apoptosis by L-carnitine through inhibition of the fatty acid-induced cytochrome c release.
心血管风险常伴有血清脂肪酸水平升高。虽然最近的研究表明脂肪酸会影响线粒体功能并诱导细胞凋亡，但左旋肉碱对于脂肪酸被线粒体摄取是必不可少的，它可能会减轻心肌细胞的线粒体功能障碍和凋亡。本研究旨在利用大鼠分离的心肌线粒体阐明左旋肉碱在预防脂肪酸诱导的线粒体膜通透性转换和细胞色素 c 释放中的作用。用左旋肉碱抑制了棕榈酰辅酶 A 诱导的线粒体呼吸。存在左旋肉碱时，可大大抑制棕榈酰辅酶 A 诱导的线粒体膜去极化和肿胀。在超微结构观察中，用棕榈酰辅酶 A 处理会诱导终末肿胀和破裂的线粒体，其嵴结构几乎不可辨认。然而，用左旋肉碱预处理可显著抑制心肌线粒体的严重形态损伤。即使左旋肉碱不能保护这些抑制剂引起的耗氧量下降，左旋肉碱也能减轻 4-羟基-L-苯甘氨酸和鱼藤酮诱导的线粒体肿胀。此外，左旋肉碱完全抑制了棕榈酰辅酶 A 诱导的细胞色素 c 释放。我们得出结论，左旋肉碱对于心脏线粒体在高脂肪酸β氧化存在的情况下减轻膜通透性转换、维持超微结构和膜稳定是必不可少的。因此，左旋肉碱可能通过抑制脂肪酸诱导的细胞色素 c 释放来保护细胞免受凋亡。
