Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse
Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischem...
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| Veröffentlicht in: | Experimental neurology 2017-06, Vol.292, p.46-55 |
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| creator | Ye, Xinchun Shen, Tong Hu, Jinxia Zhang, Liang Zhang, Yunshan Bao, Lei Cui, Chengcheng Jin, Guoliang Zan, Kun Zhang, Zuohui Yang, Xinxin Shi, Hongjuan Zu, Jie Yu, Ming Song, Chengjie Wang, Yulan Qi, Suhua Cui, Guiyun |
| description | Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. The expressions of P2X7R, NLRP3 inflammsome components, and cleaved caspase-3 were significantly enhanced in the ischemic brain tissue after stroke. However, the expression of cleaved caspase-3 was significantly attenuated after treatment of stroke with P2X7R antagonist (BBG) or NLRP3 inhibitor (MCC950). The treatment also significantly reduced the infarction volume, neuronal apoptosis, and neurological impairment. In addition, in vitro data also support the hypothesis that P2X7R/NLRP3 pathway plays a vital role in caspase-3 dependent neuronal apoptosis after ischemic stroke. Further investigation of effective regulation of P2X7R and NLRP3 in stroke is warranted.
•The expressions of P2X7R, NLRP3 inflammsome components were increased after stroke.•BBG treatment reduced neurological impairment, neuronal apoptosis.•MCC950 treatment also reduced neurological impairment, neuronal apoptosis.•NLRP3 mediated neuronal apoptosis could be ameliorated by a P2X7R antagonist.•In vitro data also supported that P2X7R/NLRP3 pathway triggers neuronal apoptosis. |
| doi_str_mv | 10.1016/j.expneurol.2017.03.002 |
| format | Article |
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•The expressions of P2X7R, NLRP3 inflammsome components were increased after stroke.•BBG treatment reduced neurological impairment, neuronal apoptosis.•MCC950 treatment also reduced neurological impairment, neuronal apoptosis.•NLRP3 mediated neuronal apoptosis could be ameliorated by a P2X7R antagonist.•In vitro data also supported that P2X7R/NLRP3 pathway triggers neuronal apoptosis.</description><identifier>ISSN: 0014-4886</identifier><identifier>EISSN: 1090-2430</identifier><identifier>DOI: 10.1016/j.expneurol.2017.03.002</identifier><identifier>PMID: 28274860</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Apoptosis - physiology ; Apoptosis Regulatory Proteins - metabolism ; Carrier Proteins - metabolism ; Caspase-3 ; Cells, Cultured ; Disease Models, Animal ; Inflammasomes - metabolism ; Ischemia - metabolism ; Ischemic stroke ; Male ; Mice, Inbred C57BL ; Neuronal apoptosis ; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism ; NLRP3 inflammasome ; P2X7 receptor ; Receptors, Purinergic - metabolism ; Signal Transduction - physiology ; Stroke - metabolism</subject><ispartof>Experimental neurology, 2017-06, Vol.292, p.46-55</ispartof><rights>2017</rights><rights>Copyright © 2017. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c425t-abe9ed40e01daf9406d3f1ce3064ac4218c6eb424958bee794774d2c55c925d13</citedby><cites>FETCH-LOGICAL-c425t-abe9ed40e01daf9406d3f1ce3064ac4218c6eb424958bee794774d2c55c925d13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.expneurol.2017.03.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28274860$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ye, Xinchun</creatorcontrib><creatorcontrib>Shen, Tong</creatorcontrib><creatorcontrib>Hu, Jinxia</creatorcontrib><creatorcontrib>Zhang, Liang</creatorcontrib><creatorcontrib>Zhang, Yunshan</creatorcontrib><creatorcontrib>Bao, Lei</creatorcontrib><creatorcontrib>Cui, Chengcheng</creatorcontrib><creatorcontrib>Jin, Guoliang</creatorcontrib><creatorcontrib>Zan, Kun</creatorcontrib><creatorcontrib>Zhang, Zuohui</creatorcontrib><creatorcontrib>Yang, Xinxin</creatorcontrib><creatorcontrib>Shi, Hongjuan</creatorcontrib><creatorcontrib>Zu, Jie</creatorcontrib><creatorcontrib>Yu, Ming</creatorcontrib><creatorcontrib>Song, Chengjie</creatorcontrib><creatorcontrib>Wang, Yulan</creatorcontrib><creatorcontrib>Qi, Suhua</creatorcontrib><creatorcontrib>Cui, Guiyun</creatorcontrib><title>Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse</title><title>Experimental neurology</title><addtitle>Exp Neurol</addtitle><description>Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. The expressions of P2X7R, NLRP3 inflammsome components, and cleaved caspase-3 were significantly enhanced in the ischemic brain tissue after stroke. However, the expression of cleaved caspase-3 was significantly attenuated after treatment of stroke with P2X7R antagonist (BBG) or NLRP3 inhibitor (MCC950). The treatment also significantly reduced the infarction volume, neuronal apoptosis, and neurological impairment. In addition, in vitro data also support the hypothesis that P2X7R/NLRP3 pathway plays a vital role in caspase-3 dependent neuronal apoptosis after ischemic stroke. Further investigation of effective regulation of P2X7R and NLRP3 in stroke is warranted.
•The expressions of P2X7R, NLRP3 inflammsome components were increased after stroke.•BBG treatment reduced neurological impairment, neuronal apoptosis.•MCC950 treatment also reduced neurological impairment, neuronal apoptosis.•NLRP3 mediated neuronal apoptosis could be ameliorated by a P2X7R antagonist.•In vitro data also supported that P2X7R/NLRP3 pathway triggers neuronal apoptosis.</description><subject>Animals</subject><subject>Apoptosis - physiology</subject><subject>Apoptosis Regulatory Proteins - metabolism</subject><subject>Carrier Proteins - metabolism</subject><subject>Caspase-3</subject><subject>Cells, Cultured</subject><subject>Disease Models, Animal</subject><subject>Inflammasomes - metabolism</subject><subject>Ischemia - metabolism</subject><subject>Ischemic stroke</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Neuronal apoptosis</subject><subject>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</subject><subject>NLRP3 inflammasome</subject><subject>P2X7 receptor</subject><subject>Receptors, Purinergic - metabolism</subject><subject>Signal Transduction - physiology</subject><subject>Stroke - metabolism</subject><issn>0014-4886</issn><issn>1090-2430</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkE1P3DAQhq2qVdnS_oXiYy8JY8eJ4yNCtCCtKKpaqTfLa092veQL22nh32O6wLWnuTzzvjMPIScMSgasOd2XeD-PuISpLzkwWUJVAvA3ZMVAQcFFBW_JCoCJQrRtc0Q-xLgHACW4fE-OeMulaBtYEXezBD9i2HpL-W9JA1qc0xROr9c_bio6m7T7ax5oCn67xRDpv87R9NTMU-aij9R0CQP10e5wyCkxhekWqR9p2iEdpiXiR_KuM33ET8_zmPz6evHz_LJYf_92dX62LqzgdSrMBhU6AQjMmU4JaFzVMYsVNMJkhLW2wY3gQtXtBlEqIaVw3Na1Vbx2rDomXw65c5juFoxJD_ks7HszYr5Ds1Y2QimQkFF5QG2YYgzY6Tn4wYQHzUA_KdZ7_apYPynWUOmsOG9-fi5ZNgO6170Xpxk4OwCYX_3jMehoPY4Wnc92k3aT_2_JIwEtkts</recordid><startdate>201706</startdate><enddate>201706</enddate><creator>Ye, Xinchun</creator><creator>Shen, Tong</creator><creator>Hu, Jinxia</creator><creator>Zhang, Liang</creator><creator>Zhang, Yunshan</creator><creator>Bao, Lei</creator><creator>Cui, Chengcheng</creator><creator>Jin, Guoliang</creator><creator>Zan, Kun</creator><creator>Zhang, Zuohui</creator><creator>Yang, Xinxin</creator><creator>Shi, Hongjuan</creator><creator>Zu, Jie</creator><creator>Yu, Ming</creator><creator>Song, Chengjie</creator><creator>Wang, Yulan</creator><creator>Qi, Suhua</creator><creator>Cui, Guiyun</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201706</creationdate><title>Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse</title><author>Ye, Xinchun ; Shen, Tong ; Hu, Jinxia ; Zhang, Liang ; Zhang, Yunshan ; Bao, Lei ; Cui, Chengcheng ; Jin, Guoliang ; Zan, Kun ; Zhang, Zuohui ; Yang, Xinxin ; Shi, Hongjuan ; Zu, Jie ; Yu, Ming ; Song, Chengjie ; Wang, Yulan ; Qi, Suhua ; Cui, Guiyun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c425t-abe9ed40e01daf9406d3f1ce3064ac4218c6eb424958bee794774d2c55c925d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Apoptosis - physiology</topic><topic>Apoptosis Regulatory Proteins - metabolism</topic><topic>Carrier Proteins - metabolism</topic><topic>Caspase-3</topic><topic>Cells, Cultured</topic><topic>Disease Models, Animal</topic><topic>Inflammasomes - metabolism</topic><topic>Ischemia - metabolism</topic><topic>Ischemic stroke</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Neuronal apoptosis</topic><topic>NLR Family, Pyrin Domain-Containing 3 Protein - metabolism</topic><topic>NLRP3 inflammasome</topic><topic>P2X7 receptor</topic><topic>Receptors, Purinergic - metabolism</topic><topic>Signal Transduction - physiology</topic><topic>Stroke - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ye, Xinchun</creatorcontrib><creatorcontrib>Shen, Tong</creatorcontrib><creatorcontrib>Hu, Jinxia</creatorcontrib><creatorcontrib>Zhang, Liang</creatorcontrib><creatorcontrib>Zhang, Yunshan</creatorcontrib><creatorcontrib>Bao, Lei</creatorcontrib><creatorcontrib>Cui, Chengcheng</creatorcontrib><creatorcontrib>Jin, Guoliang</creatorcontrib><creatorcontrib>Zan, Kun</creatorcontrib><creatorcontrib>Zhang, Zuohui</creatorcontrib><creatorcontrib>Yang, Xinxin</creatorcontrib><creatorcontrib>Shi, Hongjuan</creatorcontrib><creatorcontrib>Zu, Jie</creatorcontrib><creatorcontrib>Yu, Ming</creatorcontrib><creatorcontrib>Song, Chengjie</creatorcontrib><creatorcontrib>Wang, Yulan</creatorcontrib><creatorcontrib>Qi, Suhua</creatorcontrib><creatorcontrib>Cui, Guiyun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Experimental neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ye, Xinchun</au><au>Shen, Tong</au><au>Hu, Jinxia</au><au>Zhang, Liang</au><au>Zhang, Yunshan</au><au>Bao, Lei</au><au>Cui, Chengcheng</au><au>Jin, Guoliang</au><au>Zan, Kun</au><au>Zhang, Zuohui</au><au>Yang, Xinxin</au><au>Shi, Hongjuan</au><au>Zu, Jie</au><au>Yu, Ming</au><au>Song, Chengjie</au><au>Wang, Yulan</au><au>Qi, Suhua</au><au>Cui, Guiyun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse</atitle><jtitle>Experimental neurology</jtitle><addtitle>Exp Neurol</addtitle><date>2017-06</date><risdate>2017</risdate><volume>292</volume><spage>46</spage><epage>55</epage><pages>46-55</pages><issn>0014-4886</issn><eissn>1090-2430</eissn><abstract>Previous research has shown that Purinergic 2X7 receptor (P2X7R) and NLRP3 inflammasome contribute to the inflammatory activation. In this study, we investigated whether P2X7R/NLRP3 pathway is involved in the caspase-3 dependent neuronal apoptosis after ischemic stroke by using a focal cortex ischemic stroke model. The expressions of P2X7R, NLRP3 inflammsome components, and cleaved caspase-3 were significantly enhanced in the ischemic brain tissue after stroke. However, the expression of cleaved caspase-3 was significantly attenuated after treatment of stroke with P2X7R antagonist (BBG) or NLRP3 inhibitor (MCC950). The treatment also significantly reduced the infarction volume, neuronal apoptosis, and neurological impairment. In addition, in vitro data also support the hypothesis that P2X7R/NLRP3 pathway plays a vital role in caspase-3 dependent neuronal apoptosis after ischemic stroke. Further investigation of effective regulation of P2X7R and NLRP3 in stroke is warranted.
•The expressions of P2X7R, NLRP3 inflammsome components were increased after stroke.•BBG treatment reduced neurological impairment, neuronal apoptosis.•MCC950 treatment also reduced neurological impairment, neuronal apoptosis.•NLRP3 mediated neuronal apoptosis could be ameliorated by a P2X7R antagonist.•In vitro data also supported that P2X7R/NLRP3 pathway triggers neuronal apoptosis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28274860</pmid><doi>10.1016/j.expneurol.2017.03.002</doi><tpages>10</tpages></addata></record> |
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| subjects | Animals Apoptosis - physiology Apoptosis Regulatory Proteins - metabolism Carrier Proteins - metabolism Caspase-3 Cells, Cultured Disease Models, Animal Inflammasomes - metabolism Ischemia - metabolism Ischemic stroke Male Mice, Inbred C57BL Neuronal apoptosis NLR Family, Pyrin Domain-Containing 3 Protein - metabolism NLRP3 inflammasome P2X7 receptor Receptors, Purinergic - metabolism Signal Transduction - physiology Stroke - metabolism |
| title | Purinergic 2X7 receptor/NLRP3 pathway triggers neuronal apoptosis after ischemic stroke in the mouse |
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