Involvement of dopamine receptors in binge methamphetamine-induced activation of endoplasmic reticulum and mitochondrial stress pathways.
Involvement of dopamine receptors in binge methamphetamine-induced activation of endoplasmic reticulum and mitochondrial stress pathways.
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DOI：
10.1371/journal.pone.0028946
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Cadet JL
中科院分区：
文献类型：
--
作者：
Beauvais G;Atwell K;Jayanthi S;Ladenheim B;Cadet JL
单一大剂量甲基苯丙胺可引起内质网应激和啮齿类动物纹状体线粒体功能障碍。多巴胺D1受体似乎参与了这些冰毒介导的应激反应。本研究的目的是探讨多巴胺D_1和D_2受体是否参与了单日暴食冰毒引起的内质网和线粒体应激反应。雄性SD大鼠在每次注射冰毒前30分钟分别4次注射冰毒10 mg/kg或与可能的D_1或D_2受体拮抗剂SCH23390或雷氯普利联合注射。随后在不同时间点处死大鼠。纹状体组织用于定量RT-PCR和Western印迹分析。我们发现，狂欢注射冰毒以SCH23390敏感的方式增加了促生存基因Bip/GRP-78和P58IPK的表达。METH还导致内质网应激基因ATF2、ATF3、ATF4、CHOP/Gadd153和Gadd34上调。注射冰毒后热休克蛋白(HSPs)表达增加。SCH23390完全阻断了所有内质网应激相关蛋白的诱导，包括ATF3、ATF4、CHOP/Gadd153、HSPs和caspase-12。多巴胺D2类拮抗剂雷氯普利对冰毒诱导的内质网应激蛋白的某些变化有轻微到中度的抑制作用。重要的是，冰毒以SCH23390敏感的方式导致线粒体抗凋亡蛋白Bcl2的减少，但促进细胞凋亡的蛋白Bax、Bad和细胞色素c的增加。相比之下，拉氯普利仅对冰毒引起的线粒体蛋白变化有轻微的抑制作用。这些结果表明，冰毒诱导的纹状体ER和线粒体应激通路的激活可能与SCH23390敏感受体的激活更相关。
Single large doses of methamphetamine (METH) cause endoplasmic reticulum (ER) stress and mitochondrial dysfunctions in rodent striata. The dopamine D1 receptor appears to be involved in these METH-mediated stresses. The purpose of this study was to investigate if dopamine D1 and D2 receptors are involved in ER and mitochondrial stresses caused by single-day METH binges in the rat striatum. Male Sprague-Dawley rats received 4 injections of 10 mg/kg of METH alone or in combination with a putative D1 or D2 receptor antagonist, SCH23390 or raclopride, respectively, given 30 min prior to each METH injection. Rats were euthanized at various timepoints afterwards. Striatal tissues were used in quantitative RT-PCR and western blot analyses. We found that binge METH injections caused increased expression of the pro-survival genes, BiP/GRP-78 and P58IPK, in a SCH23390-sensitive manner. METH also caused up-regulation of ER-stress genes, Atf2, Atf3, Atf4, CHOP/Gadd153 and Gadd34. The expression of heat shock proteins (HSPs) was increased after METH injections. SCH23390 completely blocked induction in all analyzed ER stress-related proteins that included ATF3, ATF4, CHOP/Gadd153, HSPs and caspase-12. The dopamine D2-like antagonist, raclopride, exerted small to moderate inhibitory influence on some METH-induced changes in ER stress proteins. Importantly, METH caused decreases in the mitochondrial anti-apoptotic protein, Bcl-2, but increases in the pro-apoptotic proteins, Bax, Bad and cytochrome c, in a SCH23390-sensitive fashion. In contrast, raclopride provided only small inhibition of METH-induced changes in mitochondrial proteins. These findings indicate that METH-induced activation of striatal ER and mitochondrial stress pathways might be more related to activation of SCH23390-sensitive receptors.
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影响因子：
16
作者：
Harding, HP;Zhang, YH;Ron, D
通讯作者：
Ron, D
DOI：
10.1073/pnas.88.9.3720
发表时间：
1991-05-01
影响因子：
11.1
作者：
HAI, T;CURRAN, T
通讯作者：
CURRAN, T
DOI：
10.1016/s0169-328x(01)00184-x
发表时间：
2001-09-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Deng, XL;Wang, Y;Cadet, JL
通讯作者：
Cadet, JL
影响因子：
1.5
作者：
Adachi, Yusuke;Yamamoto, Keisuke;Mori, Kazutoshi
通讯作者：
Mori, Kazutoshi
DOI：
10.1124/jpet.109.159244
发表时间：
2010-03-01
影响因子：
3.5
作者：
Hayashi, Teruo;Justinova, Zuzana;Su, Tsung-Ping
通讯作者：
Su, Tsung-Ping