Separovic Duska, Wang Shouye, Awad Maitah Ma'In Yehya, Hanada Kentaro, Kessel David
Department of Fundamental and Applied Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
Biochem Biophys Res Commun. 2006 Jun 30;345(2):803-8. doi: 10.1016/j.bbrc.2006.04.131. Epub 2006 May 2.
The oxidative stress induced by photodynamic therapy using the phthalocyanine Pc 4 (PDT) can lead to apoptosis, and is accompanied by photodamage to Bcl-2 and accumulation of de novo ceramide. Similar to PDT, the oxidative stress inducer and Bcl-2 inhibitor HA14-1 triggers apoptosis. To test the specificity of the ceramide response, Jurkat cells were exposed to an equitoxic dose of HA14-1. Unlike PDT, HA14-1 did not induce accumulation of de novo ceramide, although levels of sphingomyelin, phosphatidylserine and phosphatidylethanolamine were below control values after either treatment. In contrast to PDT, (i) the transient inhibition of serine palmitoyltransferase induced by HA14-1 was associated with the initial decrease in de novo ceramide, and (ii) HA14-1-initiated inhibition of sphingomyelin synthase and glucosylceramide synthase did not result in accumulation of de novo ceramide. These results show that the ceramide response to PDT is not induced by another pro-apoptotic stimulus, and may be unique to PDT as described here.
使用酞菁Pc 4进行光动力疗法（PDT）所诱导的氧化应激可导致细胞凋亡，并伴有对Bcl-2的光损伤以及新合成神经酰胺的积累。与PDT类似，氧化应激诱导剂及Bcl-2抑制剂HA14-1可触发细胞凋亡。为测试神经酰胺反应的特异性，将Jurkat细胞暴露于等毒性剂量的HA14-1。与PDT不同，HA14-1并未诱导新合成神经酰胺的积累，尽管两种处理后鞘磷脂、磷脂酰丝氨酸和磷脂酰乙醇胺的水平均低于对照值。与PDT相反，（i）HA14-1所诱导的丝氨酸棕榈酰转移酶的短暂抑制与新合成神经酰胺的初始减少有关，且（ii）HA14-1引发的鞘磷脂合酶和葡糖神经酰胺合酶的抑制并未导致新合成神经酰胺的积累。这些结果表明，对PDT的神经酰胺反应并非由另一种促凋亡刺激所诱导，且可能如本文所述，是PDT所特有的。
