Concentration-dependent opposite effects of 1-benzyl-1,2,3,4-tetrahydroisoquinoline on markers of apoptosis: in vitro and ex vivo studies.
Concentration-dependent opposite effects of 1-benzyl-1,2,3,4-tetrahydroisoquinoline on markers of apoptosis: in vitro and ex vivo studies.
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DOI：
10.1007/s12640-013-9436-x
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发表时间：
2014-01
影响因子：
3.7
通讯作者：
Antkiewicz-Michaluk L
中科院分区：
文献类型：
--
作者：
Wąsik A;Kajta M;Lenda T;Antkiewicz-Michaluk L
1-苄基-1，2，3，4-四氢异喹啉（1-Benzyl-1，2，3，4-tetrahydroisoquinoline，1BnTIQ）对多巴胺能神经元具有神经毒性，被认为是导致帕金森病的内源性危险因素。为了更好地理解1BnTIQ产生毒性的分子机制，我们检查了不同浓度的1BnTIQ（50、100和500 μM）对谷氨酸诱导的凋亡途径的影响。我们测量了凋亡的标志物，如caspase-3活性，乳酸脱氢酶释放和线粒体膜电位。通过钙黄绿素AM和Hoechst 33342染色在细胞水平上支持分子数据。所获得的数据证明了1BnTIQ对抗细胞凋亡的浓度依赖性作用，并且证明了低浓度（50 μM）的1BnTIQ表现出神经保护活性，而10倍高浓度（500 μM）的1BnTIQ可能具有神经毒性，并且显著增强了谷氨酸诱导的细胞凋亡标记物的增加。此外，使用离体分子研究，我们表明，急性和慢性给药1BnTIQ不影响大鼠黑质中α突触核蛋白和酪氨酸羟化酶蛋白的水平。总结这些研究，我们认为1BnTIQ是一种相当弱的内源性神经毒素;然而，应该考虑到，在较高的μ mol浓度下，它可以启动中枢神经系统的凋亡，并可能参与神经退行性疾病的发病机制。
1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ) was shown to be neurotoxic to the dopaminergic neurons, and thus it was proposed to be an endogenous risk factor leading to Parkinson’s disease. In order to better understand the molecular mechanisms of 1BnTIQ—produced toxicity, we examined the impact of different concentrations of 1BnTIQ (50, 100, and 500 μM) on glutamate-induced apoptotic pathway. We measured the markers of apoptosis, such as caspase-3 activity, lactate dehydrogenase release, and mitochondrial membrane potential. Molecular data were supported at the cellular level by calcein AM and Hoechst 33342 staining. The obtained data demonstrated concentration-dependent effects of 1BnTIQ opposing apoptosis, and evidenced that 1BnTIQ in a low concentration (50 μM) exhibited neuroprotective activity, whereas in 10 times higher concentration (500 μM) might be neurotoxic, and significantly intensified glutamate-induced increase in apoptosis markers. Additionally, using an ex vivo molecular study we indicated that both acute and chronic administration of 1BnTIQ did not affect the level of alpha synuclein and tyrosine hydroxylase protein in the rat substantia nigra. Summarizing the studies, we suggest that 1BnTIQ is a rather weak endogenous neurotoxin; however, it should be taken into account that in higher μmoles concentrations, it can initiate apoptosis in the central nervous system and may be involved in the etiopathology of neurodegenerative diseases.
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影响因子：
3.3
作者：
Kajta, M.;Wojtowicz, A. K.;Lason, W.
通讯作者：
Lason, W.
影响因子：
3.3
作者：
Kajta, M.;Rzemieniec, J.;Wojtowicz, A. K.
通讯作者：
Wojtowicz, A. K.
影响因子：
4.8
作者：
Bayir, Huelya;Kapralov, Alexandr A.;Kagan, Valerian E.
通讯作者：
Kagan, Valerian E.
影响因子：
4.7
作者：
Antkiewicz-Michaluk, L;Michaluk, J;Vetulani, J
通讯作者：
Vetulani, J
影响因子：
5.3
作者：
Morishima, Y;Gotoh, Y;Greenberg, ME
通讯作者：
Greenberg, ME