Protective efficacy of carnosic acid against hydrogen peroxide induced oxidative injury in HepG2 cells through the SIRT1 pathway
Protective efficacy of carnosic acid against hydrogen peroxide induced oxidative injury in HepG2 cells through the SIRT1 pathway
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鼠尾草酸通过 SIRT1 途径对过氧化氢诱导的 HepG2 细胞氧化损伤的保护作用
DOI：
10.1139/cjpp-2014-0513
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发表时间：
2015-08-01
影响因子：
2.1
通讯作者：
Yao, Jihong
中科院分区：
文献类型：
--
作者：
Hu, Yan;Zhang, Ning;Yao, Jihong
鼠尾草酸（CA），发现在迷迭香，已被报道具有抗氧化剂和抗脂肪形成的特性。在这里，我们研究了CA抑制过氧化氢（H2 O2）诱导的HepG 2细胞损伤的分子机制。用2.5-10 μ mol/L CA预处理细胞2 h，然后再暴露于3 mmol/L H2 O2 4 h。CA剂量依赖性地增加细胞活力和降低乳酸脱氢酶活性。预处理与CA完全衰减锰超氧化物歧化酶（MnSOD）和超大B细胞淋巴瘤（Bcl-xL）的表达抑制，并减少谷胱甘肽活性引起的H2 O2，而它逆转活性氧积累和增加裂解caspase-3。重要的是，去乙酰化酶1（SIRT 1），NAD（+）依赖性脱乙酰酶，显着增加CA。综上所述，我们推测SIRT 1可能在CA对H2 O2诱导的损伤的保护作用中发挥重要作用。正如预期的那样，Ex 527（6-氯-2，3，4，9-四氢-1H-咔唑-1-甲酰胺）对SIRT 1的抑制和siRNA介导的SIRT 1沉默（si-SIRT 1）显着加剧了H2 O2诱导的切割caspase-3水平的增加，但大大降低了MnSOD和Bcl-xL的表达下降。此外，CA的正调节作用被si-SIRT 1抑制。总的来说，本研究表明，CA可以减轻H2 O2诱导的肝细胞损伤通过SIRT 1途径。
Carnosic acid (CA), found in rosemary, has been reported to have antioxidant and antiadipogenic properties. Here, we investigate the molecular mechanism by which CA inhibits hydrogen peroxide (H2O2)-induced injury in HepG2 cells. Cells were pretreated with 2.5-10 mu mol/L CA for 2 h and then exposed to 3 mmol/L H2O2 for an additional 4 h. CA dose-dependently increased cell viability and decreased lactate dehydrogenase activities. Pretreatment with CA completely attenuated the inhibited expression of manganese superoxide dismutase (MnSOD) and the B-cell lymphoma-extra large (Bcl-xL), and reduced glutathione activity caused by H2O2, whereas it reversed reactive oxygen species accumulation and the increase in cleaved caspase-3. Importantly, sirtuin 1 (SIRT1), a NAD(+)-dependent deacetylase, was significantly increased by CA. Considering the above results, we hypothesized that SIRT1 may play important roles in the protective effects of CA in injury induced by H2O2. As expected, SIRT1 suppression by Ex527 (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide) and siRNA-mediated SIRT1 silencing (si-SIRT1) significantly aggravated the H2O2-induced increased level of cleaved caspase-3 but greatly reduced the decreased expression of MnSOD and Bcl-xL. Furthermore, the positive regulatory effect of CA was inhibited by si-SIRT1. Collectively, the present study indicated that CA can alleviate H2O2-induced hepatocyte damage through the SIRT1 pathway.