Deficiency in the inner mitochondrial membrane peptidase 2-like (Immp21) gene increases ischemic brain damage and impairs mitochondrial function

NEUROBIOLOGY OF DISEASE

卷:44

Article

Ma, Yi^1,2  Mehta, Suresh L.¹  Lu, Baisong³  Li, P. Andy¹ 

[1] N Carolina Cent Univ, Dept Pharmaceut Sci, BRITE, Durham, NC 27707 USA

[2] Ningxia Med Univ, Dept Pathol, Ningxia, Peoples R China

[3] Wake Forest Univ, Inst Regenerat Med, Sch Med, Winston Salem, NC 27109 USA

关键词: Cerebral ischemia;    Cell death mechanisms;    Focal ischemia;    Gene regulation;    Immp21;    Immunohistochemistry;    Mitochondria;    Reperfusion;   

DOI  :  10.1016/j.nbd.2011.06.019

来源: Elsevier

【 摘 要 】

Mitochondrial dysfunction plays an important role in mediating ischemic brain damage. Immp21 is an inner mitochondrial membrane peptidase that processes mitochondrial protein cytochrome c1 (Cycl). Homozygous mutation of Immp21 (Immp21(Tg(Tyr)979Ove) or Immp21(-/-)) elevates mitochondrial membrane potential, increases superoxide (center dot O(2)(-)) production in the brain and impairs fertility. The objectives of this study are to explore the effects of heterozygous mutation of Immp21(Immp21(+/-)) on ischemic outcome and to determine the influence of Immp21 deficiency on brain mitochondria after stroke. Male Immp21(+/-) and wild-type (WT) mice were subjected to 1-h focal cerebral ischemia. Their brains were harvested after 5 and 24-h of reperfusion. The results showed that infarct volume and DNA oxidative damage significantly increased in the Immp21(+/-) mice. There were no obvious cerebral vasculature abnormalities between the two types of mice viewed by Indian ink perfusion. The increased damage in Immp21(+/-) mice was associated with early increase in center dot O(2)(-) production. Mitochondrial respiratory rate, total mitochondrial respiratory capacity and mitochondrial respiratory complex activities were decreased at 5-h of recirculation in Immp21(+/-) mice compared to WT mice. Our results suggest that Immp21 deficiency increases ischemic brain damage by enhancing center dot O(2)(-) production and damaging mitochondrial functional performance. Published by Elsevier Inc.

【 授权许可】

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