Pannexins in ischemia-induced neurodegeneration

被引：190

作者：

Bargiotas, Panagiotis ^{[1
,2
,3
]}

Krenz, Antje ^{[3
]}

Hormuzdi, Sheriar G. ^{[1
,5
]}

Ridder, Dirk A. ^{[2
]}

Herb, Anne ^{[1
,4
]}

Barakat, Waleed ^{[3
]}

Penuela, Silvia ^{[6
]}

von Engelhardt, Jakob ^{[1
,4
]}

Monyer, Hannah ^{[1
,4
]}

Schwaninger, Markus ^{[2
,3
]}

机构：

[1] Univ Heidelberg, Dept Clin Neurobiol, D-69120 Heidelberg, Germany

[2] Univ Lubeck, Inst Expt & Clin Pharmacol & Toxicol, D-23538 Lubeck, Germany

[3] Univ Heidelberg, Dept Pharmacol, D-69120 Heidelberg, Germany

[4] German Canc Res Ctr, D-69120 Heidelberg, Germany

[5] Univ Dundee, Ninewells Hosp & Med Sch, Ctr Neurosci, Dundee DD1 9SY, Scotland

[6] Univ Western Ontario, Dept Anat & Cell Biol, London, ON N6A 5C1, Canada

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 51期

关键词：

ATP release; gap junctions; macrophage; middle cerebral artery occlusion; metabolic inhibition; OXYGEN GLUCOSE DEPRIVATION; GAP-JUNCTION HEMICHANNELS; SPREADING DEPRESSION; CEREBRAL-ISCHEMIA; ATP RELEASE; INTERLEUKIN-1-BETA RELEASE; GLOBAL-ISCHEMIA; P2X(7) RECEPTOR; IN-VITRO; CHANNELS;

D O I：

10.1073/pnas.1018262108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Pannexin 1 (Px1, Panx1) and pannexin 2 (Px2, Panx2) form large-pore nonselective channels in the plasma membrane of cells and were suggested to play a role in the pathophysiology of cerebral ischemia. To directly test a potential contribution of pannexins in ischemia-related mechanisms, we performed experiments in Px1(-/-), Px2(-/-), and Px1(-/-) Px2(-/-) knockout mice. IL-1 beta release, channel function in astrocytes, and cortical spreading depolarization were not altered in Px1(-/-) Px2(-/-) mice, indicating that, in contrast to previous concepts, these processes occur normally in the absence of pannexin channels. However, ischemia-induced dye release from cortical neurons was lower, indicating that channel function in Px1(-/-) Px2(-/-) neurons was impaired. Furthermore, Px1(-/-) Px2(-/-) mice had a better functional outcome and smaller infarcts than wild-type mice when subjected to ischemic stroke. In conclusion, our data demonstrate that Px1 and Px2 underlie channel function in neurons and contribute to ischemic brain damage.

引用

页码：20772 / 20777

页数：6

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