Overexpression of mitochondrial uncoupling protein 2 inhibits inflammatory cytokines and activates cell survival factors after cerebral ischemia.

PloS One
Bryan A Haines, P Andy Li

Abstract

Mitochondria play a critical role in cell survival and death after cerebral ischemia. Uncoupling proteins (UCPs) are inner mitochondrial membrane proteins that disperse the mitochondrial proton gradient by translocating H(+) across the inner membrane in order to stabilize the inner mitochondrial membrane potential (ΔΨ(m)) and reduce the formation of reactive oxygen species. Previous studies have demonstrated that mice transgenically overexpressing UCP2 (UCP2 Tg) in the brain are protected from cerebral ischemia, traumatic brain injury and epileptic challenges. This study seeks to clarify the mechanisms responsible for neuroprotection after transient focal ischemia. Our hypothesis is that UCP2 is neuroprotective by suppressing innate inflammation and regulating cell cycle mediators. PCR gene arrays and protein arrays were used to determine mechanisms of damage and protection after transient focal ischemia. Our results showed that ischemia increased the expression of inflammatory genes and suppressed the expression of anti-apoptotic and cell cycle genes. Overexpression of UCP2 blunted the ischemia-induced increase in IL-6 and decrease in Bcl2. Further, UCP2 increased the expression of cell cycle genes and protein levels of phosph...Continue Reading

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Citations

Jun 27, 2013·Alcoholism, Clinical and Experimental Research·Jan A GrawClaudia D Spies
Jan 29, 2016·Brain Circulation·Kevin B Koronowski, Miguel A Perez-Pinzon
Jan 21, 2018·Antioxidants & Redox Signaling·Petr JežekMartin Jabůrek
Sep 30, 2014·Journal of Bioenergetics and Biomembranes·John W ThompsonMiguel A Perez-Pinzon
Nov 9, 2019·Molecular Medicine Reports·Wanwan PengQiyi Zeng
Aug 31, 2018·Oxidative Medicine and Cellular Longevity·Marina Rascio Henriques DutraJosé Antônio Silva

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Methods Mentioned

BETA
genetic knockout
PCR
protein array
dissection

Software Mentioned

SuperArray
NIH
RT 2 Profiler⢠Excel

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