Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ischemic stroke is one of the most frequent acute cerebrovascular events worldwide. This study evaluated the variability of AMPK and mTOR and their relevance on LC3 and Beclin-1 expression, and further expounded the possible protective mechanism of inhibiting AMPK activity in the cerebral cortex after permanent focal cerebral ischemia injury in mice. Western blot and immunohistochemistry showed that p-AMPK expression was low in the cerebral cortex of the sham group; whereas it was significantly increased at 3h and 6h and peaked at 3h after pMCAO in the cerebral ischemic cortex, and was decreased at 12h and 24h. The expression patterns of LC3 and Beclin-1 were the same as that of p-AMPK after occlusion, and the variability pattern between p-AMPK and p-mTOR levels was completely inverted. After treatment with the AMPK inhibitor Compound C, p-AMPK/LC3/Beclin-1 expression was decreased significantly, whereas p-mTOR level was increased significantly. Deficiency of Nissl bodies was reduced compared with that in the vehicle group at all times points after occlusion. Neurological deficits, infarct areas, and brain water content were also significantly reduced 24h after occlusion with compound C treatment. The results suggested that the AMPK-autophagy pathway was activated, concomitant with mTOR inhibition in cerebral cortex after ischemic injury in mice. Moreover, inhibition of AMPK activity by Compound C inhibited autophagy and conferred protection against brain damage by restoring mTOR activity.
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PMID:Inhibition of AMP-activated protein kinase alleviates focal cerebral ischemia injury in mice: Interference with mTOR and autophagy. 2756 85

Ischemic stroke initiated by transient or permanent cerebral blood flow decline remains the leading cause of permanent disability in industrialized nations. Therapeutic strategies to improve patient recovery are remain limited. Hypoxia post-conditioning (HPostC) has been known to be neuroprotective against ischemic injuries in vivo and in vitro. Understanding its mechanism of action may promote its clinical translation. In this study, we devised a method of HPostC treatment to provide protection from a focal cerebral ischemic induced injury and to explore the underling mechanism. We found that our HPostC method improved energy supply by elevating the level of glucose, pyruvate and ATP/ADP ratio within the cerebral hemisphere in mice. In the distal middle cerebral artery occlusion (dMCAO) mice, this HPostC treatment reduced infarct size, and was associated with increased levels of pyruvate, pyruvate/lactate ratio and ATP/ADP ratio. Western blot analysis indicated that the HPostC treatment up-regulated AMPK signaling activities in the cerebral hemisphere. Our results suggest that this HPostC treatment exerts its neuroprotective effect by promoting glycolysis to elevate the ATP/ADP level, and the AMPK/PFKFB3 signaling pathway. These findings may provide biomarkers for clinical use of HPostC methods.
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PMID:Hypoxia post-conditioning promoted glycolysis in mice cerebral ischemic model. 3276 37