Curcumin pretreatment induces Nrf2 and an antioxidant response and prevents hemin-induced toxicity in primary cultures of cerebellar granule neurons of rats.
Curcumin pretreatment induces Nrf2 and an antioxidant response and prevents hemin-induced toxicity in primary cultures of cerebellar granule neurons of rats.
复制标题
DOI：
10.1155/2013/801418
复制
发表时间：
2013
影响因子：
--
通讯作者：
Pedraza-Chaverri J
中科院分区：
文献类型：
--
作者：
González-Reyes S;Guzmán-Beltrán S;Medina-Campos ON;Pedraza-Chaverri J
姜黄素是从姜黄中提取的一种双功能抗氧化剂。本研究确定姜黄素作为一种神经保护剂，对氯化血红素诱导的大鼠小脑颗粒神经元（CGNs）的原代培养的损害。氯化血红素是血红素的氧化形式，是一种高度反应性的化合物，可诱导细胞损伤。用5-30 μM姜黄素预处理CGN有效地增加了2.3-4.9倍血红素加氧酶-1（HO-1）表达和5.6-14.3倍谷胱甘肽（GSH）水平。此外，15 μM姜黄素使活性氧（ROS）产生的增加减少了55%，GSH/谷胱甘肽二硫化物（GSSG）比率的减少减少了94%，并使氯化血红素诱导的细胞死亡减少了49%。抑制血红素加氧酶系统或谷胱甘肽合成与锡mesoporphyrin和丁硫氨酸亚砜亚胺，分别抑制姜黄素对氯化血红素诱导的毒性的保护作用。这些数据强烈表明HO-1和GSH在姜黄素的保护作用中起主要作用。此外，发现与姜黄素孵育24小时分别使谷胱甘肽还原酶、谷胱甘肽S-转移酶和超氧化物歧化酶的活性增加1.4倍、2.3倍和5.2倍。此外，发现姜黄素能够诱导核因子（红细胞衍生2）样2（Nrf 2）易位到细胞核中。这些数据表明，姜黄素预处理诱导Nrf 2和抗氧化反应，可能发挥重要作用，这种抗氧化剂对氯化血红素诱导的神经元死亡的保护作用。
Curcumin is a bifunctional antioxidant derived from Curcuma longa. This study identifies curcumin as a neuroprotectant against hemin-induced damage in primary cultures of cerebellar granule neurons (CGNs) of rats. Hemin, the oxidized form of heme, is a highly reactive compound that induces cellular injury. Pretreatment of CGNs with 5–30 μM curcumin effectively increased by 2.3–4.9 fold heme oxygenase-1 (HO-1) expression and by 5.6–14.3-fold glutathione (GSH) levels. Moreover, 15 μM curcumin attenuated by 55% the increase in reactive oxygen species (ROS) production, by 94% the reduction of GSH/glutathione disulfide (GSSG) ratio, and by 49% the cell death induced by hemin. The inhibition of heme oxygenase system or GSH synthesis with tin mesoporphyrin and buthionine sulfoximine, respectively, suppressed the protective effect of curcumin against hemin-induced toxicity. These data strongly suggest that HO-1 and GSH play a major role in the protective effect of curcumin. Furthermore, it was found that 24 h of incubation with curcumin increases by 1.4-, 2.3-, and 5.2-fold the activity of glutathione reductase, glutathione S-transferase and superoxide dismutase, respectively. Additionally, it was found that curcumin was capable of inducing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus. These data suggest that the pretreatment with curcumin induces Nrf2 and an antioxidant response that may play an important role in the protective effect of this antioxidant against hemin-induced neuronal death.
登录
查看更多内容
影响因子：
11.4
作者：
Cristina Anderica-Romero, Ana;Gabriela Gonzalez-Herrera, Irma;Santamaria, Abel;Pedraza-Chaverri, Jose
通讯作者：
Pedraza-Chaverri, Jose
影响因子：
6.2
作者：
Dang, Theresa N.;Bishop, Glenda M.;Robinson, Stephen R.
通讯作者：
Robinson, Stephen R.
影响因子：
5.2
作者：
Lima, Cristovao F.;Pereira-Wilson, Cristina;Rattan, Suresh I. S.
通讯作者：
Rattan, Suresh I. S.
影响因子：
11.9
作者：
Gupta SC;Prasad S;Kim JH;Patchva S;Webb LJ;Priyadarsini IK;Aggarwal BB
通讯作者：
Aggarwal BB
影响因子：
7.4
作者：
Correa, Francisco;Buelna-Chontal, Mabel;Zazueta, Cecilia
通讯作者：
Zazueta, Cecilia