RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39°C
Methamphetamine is one of the most prevalent drugs abused in the world. Methamphetamine abusers usually present with hyperpyrexia (39°C), hallucination and other psychiatric symptoms. However, the detailed mechanism underlying its neurotoxic action remains elusive. This study investigated the effect...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2020-01-01
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| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=5;spage=865;epage=874;aulast=Guo |
| _version_ | 1818027684044734464 |
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| author | Li-Min Guo Zhen Wang Shi-Ping Li Mi Wang Wei-Tao Yan Feng-Xia Liu Chu-Dong Wang Xu-Dong Zhang Dan Chen Jie Yan Kun Xiong |
| author_facet | Li-Min Guo Zhen Wang Shi-Ping Li Mi Wang Wei-Tao Yan Feng-Xia Liu Chu-Dong Wang Xu-Dong Zhang Dan Chen Jie Yan Kun Xiong |
| author_sort | Li-Min Guo |
| collection | DOAJ |
| description | Methamphetamine is one of the most prevalent drugs abused in the world. Methamphetamine abusers usually present with hyperpyrexia (39°C), hallucination and other psychiatric symptoms. However, the detailed mechanism underlying its neurotoxic action remains elusive. This study investigated the effects of methamphetamine + 39°C on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats. Primary cortex neurons were exposed to 1 mM methamphetamine + 39°C. Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39°C triggered obvious necrosis-like death in cultured primary cortical neurons, which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially. Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39°C for 3 hours. After pre-treatment with RIP3 inhibitor GSK’872, propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased; RIP3 and MLKL protein expression significantly decreased. Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse. Taken together, the above results suggest that methamphetamine + 39°C can induce RIP3/MLKL regulated necroptosis, thereby resulting in neurotoxicity. The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University, China (approval numbers: 2017-S026 and 2017-S033) on March 7, 2017. |
| first_indexed | 2024-12-10T04:51:48Z |
| format | Article |
| id | doaj.art-f73f45cc1006427b9ec608c0e9bf6003 |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-10T04:51:48Z |
| publishDate | 2020-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-f73f45cc1006427b9ec608c0e9bf60032022-12-22T02:01:37ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742020-01-0115586587410.4103/1673-5374.268902RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39°CLi-Min GuoZhen WangShi-Ping LiMi WangWei-Tao YanFeng-Xia LiuChu-Dong WangXu-Dong ZhangDan ChenJie YanKun XiongMethamphetamine is one of the most prevalent drugs abused in the world. Methamphetamine abusers usually present with hyperpyrexia (39°C), hallucination and other psychiatric symptoms. However, the detailed mechanism underlying its neurotoxic action remains elusive. This study investigated the effects of methamphetamine + 39°C on primary cortical neurons from the cortex of embryonic Sprague-Dawley rats. Primary cortex neurons were exposed to 1 mM methamphetamine + 39°C. Propidium iodide staining and lactate dehydrogenase release detection showed that methamphetamine + 39°C triggered obvious necrosis-like death in cultured primary cortical neurons, which could be partially inhibited by receptor-interacting protein-1 (RIP1) inhibitor Necrostatin-1 partially. Western blot assay results showed that there were increases in the expressions of receptor-interacting protein-3 (RIP3) and mixed lineage kinase domain-like protein (MLKL) in the primary cortical neurons treated with 1 mM methamphetamine + 39°C for 3 hours. After pre-treatment with RIP3 inhibitor GSK’872, propidium iodide staining and lactate dehydrogenase release detection showed that neuronal necrosis rate was significantly decreased; RIP3 and MLKL protein expression significantly decreased. Immunohistochemistry staining results also showed that the expressions of RIP3 and MLKL were up-regulated in brain specimens from humans who had died of methamphetamine abuse. Taken together, the above results suggest that methamphetamine + 39°C can induce RIP3/MLKL regulated necroptosis, thereby resulting in neurotoxicity. The study protocol was approved by the Medical Ethics Committee of the Third Xiangya Hospital of Central South University, China (approval numbers: 2017-S026 and 2017-S033) on March 7, 2017.http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=5;spage=865;epage=874;aulast=Guogsk’872; human brain tissue; hyperpyrexia; methamphetamine; mixed lineage kinase domain-like protein; necrostatin-1; necroptosis; nerve regeneration; neural regeneration; rat cortical neurons; receptor-interacting protein-3; synergistic effect |
| spellingShingle | Li-Min Guo Zhen Wang Shi-Ping Li Mi Wang Wei-Tao Yan Feng-Xia Liu Chu-Dong Wang Xu-Dong Zhang Dan Chen Jie Yan Kun Xiong RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39°C Neural Regeneration Research gsk’872; human brain tissue; hyperpyrexia; methamphetamine; mixed lineage kinase domain-like protein; necrostatin-1; necroptosis; nerve regeneration; neural regeneration; rat cortical neurons; receptor-interacting protein-3; synergistic effect |
| title | RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39°C |
| title_full | RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39°C |
| title_fullStr | RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39°C |
| title_full_unstemmed | RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39°C |
| title_short | RIP3/MLKL-mediated neuronal necroptosis induced by methamphetamine at 39°C |
| title_sort | rip3 mlkl mediated neuronal necroptosis induced by methamphetamine at 39°c |
| topic | gsk’872; human brain tissue; hyperpyrexia; methamphetamine; mixed lineage kinase domain-like protein; necrostatin-1; necroptosis; nerve regeneration; neural regeneration; rat cortical neurons; receptor-interacting protein-3; synergistic effect |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2020;volume=15;issue=5;spage=865;epage=874;aulast=Guo |
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