Jaruga E, Bielak-Zmijewska A, Sikora E, Skierski J, Radziszewska E, Piwocka K, Bartosz G
Department of Molecular Biophysics, University of Lodz, Poland.
Biochem Pharmacol. 1998 Oct 15;56(8):961-5. doi: 10.1016/s0006-2952(98)00144-0.
Curcumin (CUR) is a natural yellow dye with antioxidant and scavenging properties present in Curcuma species. It is widely used as an anti-inflammatory, anti-mutagenic and chemopreventive agent. In addition to its inhibitory effect on proliferation, CUR has recently been shown to block dexamethasone-induced programmed cell death (apoptosis) of rat thymocytes. Because cellular thiols seem to play a role in redox regulation of apoptosis, the mechanism of the anti-apoptotic effect of CUR was studied by examining the levels of glutathione and acid-soluble sulfhydryl groups. CUR was shown to prevent the glutathione loss occurring in dexamethasone-treated thymocytes, enhancing intracellular glutathione content at 8 hr to 192% of that of nontreated cells. A 60% increase in acid-soluble sulfhydryl groups was also observed. In the presence of L-buthionine S,R-sulfoximine (BSO, an inhibitor of glutathione synthesis), intracellular glutathione content of thymocytes treated with dexamethasone and CUR fell to 31% and that of the acid-soluble sulfhydryl groups to 23% of control after 8 hr. Unexpectedly, the electrophoretic and flow cytometric studies of DNA fragmentation demonstrated that apoptosis did not occur even after 20 hr of incubation with buthionine S,R-sulfoximine and dexamethasone, while control thymocytes and the cells treated only with buthionine S,R-sulfoximine showed DNA fragmentation at a level corresponding to spontaneous apoptosis. These results show that CUR treatment elevated the concentrations of glutathione and nonprotein sulfhydryl groups, thus preventing their decrease in apoptotic thymocytes. Coadministration of L-buthionine S,R-sulfoximine and CUR did not affect the anti-apoptotic effect of CUR suggesting a glutathione-independent mechanism of cell protection.
姜黄素（CUR）是姜黄属植物中存在的一种具有抗氧化和清除特性的天然黄色染料。它被广泛用作抗炎、抗诱变和化学预防剂。除了对增殖的抑制作用外，最近还发现CUR可阻断地塞米松诱导的大鼠胸腺细胞程序性细胞死亡（凋亡）。由于细胞内硫醇似乎在凋亡的氧化还原调节中起作用，因此通过检测谷胱甘肽和酸溶性巯基的水平来研究CUR抗凋亡作用的机制。结果表明，CUR可防止地塞米松处理的胸腺细胞中谷胱甘肽的丢失，使8小时时细胞内谷胱甘肽含量增加至未处理细胞的192%。酸溶性巯基也增加了60%。在L-丁硫氨酸S，R-亚砜亚胺（BSO，谷胱甘肽合成抑制剂）存在的情况下，地塞米松和CUR处理的胸腺细胞在8小时后细胞内谷胱甘肽含量降至对照的31%，酸溶性巯基降至对照的23%。出乎意料的是，DNA片段化的电泳和流式细胞术研究表明，即使与丁硫氨酸S，R-亚砜亚胺和地塞米松孵育20小时后也未发生凋亡，而对照胸腺细胞和仅用丁硫氨酸S，R-亚砜亚胺处理的细胞显示出与自发凋亡相应水平的DNA片段化。这些结果表明，CUR处理提高了谷胱甘肽和非蛋白巯基的浓度，从而防止它们在凋亡胸腺细胞中的减少。L-丁硫氨酸S，R-亚砜亚胺与CUR共同给药并不影响CUR 的抗凋亡作用，提示细胞保护机制不依赖于谷胱甘肽。
