Dataset Information

Down-regulation of MIF by NF?B under hypoxia accelerated neuronal loss during stroke.

ABSTRACT: Neuronal apoptosis is one of the major causes of poststroke neurological deficits. Inflammation during the acute phase of stroke results in nuclear translocation of NF?B in affected cells in the infarct area. Macrophage migration inhibitory factor (MIF) promotes cardiomyocyte survival in mice following heart ischemia. However, the role of MIF during stroke remains limited. In this study, we showed that MIF expression is down-regulated by 0.75 ± 0.10-fold of the control in the infarct area in the mouse brains. Two functional cis-acing NF?B response elements were identified in the human MIF promoter. Dual activation of hypoxia and NF?B signaling resulted in significant reduction of MIF promoter activity to 0.86 ± 0.01-fold of the control. Furthermore, MIF reduced caspase-3 activation and protected neurons from oxidative stress- and in vitro ischemia/reperfusion-induced apoptosis. H2O2 significantly induced cell death with 12.81 ± 0.58-fold increase of TUNEL-positive cells, and overexpression of MIF blocked the H2O2-induced cell death. Disruption of the MIF gene in MIF-knockout mice resulted in caspase-3 activation, neuronal loss, and increased infarct development during stroke in vivo. The infarct volume was increased from 6.51 ± 0.74% in the wild-type mice to 9.07 ± 0.66% in the MIF-knockout mice. Our study demonstrates that MIF exerts a neuronal protective effect and that down-regulation of MIF by NF?B-mediated signaling under hypoxia accelerates neuronal loss during stroke. Our results suggest that MIF is an important molecule for preserving a longer time window for stroke treatment, and strategies to maintain MIF expression at physiological level could have beneficial effects for stroke patients.

SUBMITTER: Zhang S

PROVIDER: S-EPMC4202111 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Down-regulation of MIF by NFκB under hypoxia accelerated neuronal loss during stroke.

Zhang Si S Zis Odysseus O Ly Philip T T PT Wu Yili Y Zhang Shuting S Zhang Mingming M Cai Fang F Bucala Richard R Shyu Woei-Cherng WC Song Weihong W

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20140626 10

Neuronal apoptosis is one of the major causes of poststroke neurological deficits. Inflammation during the acute phase of stroke results in nuclear translocation of NFκB in affected cells in the infarct area. Macrophage migration inhibitory factor (MIF) promotes cardiomyocyte survival in mice following heart ischemia. However, the role of MIF during stroke remains limited. In this study, we showed that MIF expression is down-regulated by 0.75 ± 0.10-fold of the control in the infarct area in the ...[more]

PMID: 24970391

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Dataset Information

Down-regulation of MIF by NF?B under hypoxia accelerated neuronal loss during stroke.

Publications

Down-regulation of MIF by NFκB under hypoxia accelerated neuronal loss during stroke.

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