Research ArticlePhysiology

PERK mediates the IRES-dependent translational activation of mRNAs encoding angiogenic growth factors after ischemic stress

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Science Signaling  03 May 2016:
Vol. 9, Issue 426, pp. ra44
DOI: 10.1126/scisignal.aaf2753

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PERKing blood flow during ischemia

Oxygen deprivation of tissues occurs both physiologically, such as during exercise, and pathologically, such as during stroke or heart attack. The oxygen deprivation that occurs during ischemia causes endoplasmic reticulum (ER) stress, during which most mRNA translation is inhibited to conserve cellular resources. But in ischemic muscles, some mRNAs are translated through an alternative mechanism. These include those encoding VEGF and FGF-2, factors that stimulate blood vessel formation. Philippe et al. found that ER stress in cells and in mice activated the translation of the mRNAs for VEGF and FGF-2 through the alternative mechanism. The kinase PERK, which is activated during ER stress, mediated this translational activation. Administration of a PERK inhibitor to mice before ischemia prevented the translation of the mRNAs for VEGF and FGF-2, raising the possibility that PERK manipulation could be used to increase blood flow in ischemic tissues.

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