Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.31 (AMP-activated protein kinase)
 13,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Silent information regulator 2 (Sir2) helps survival and longevity in lower organisms during challenging situations. We investigated the possibility that Sir2alpha could be involved with brain plasticity under challenging situations. A diet high in saturated fat and sucrose, which has been shown in rodents to reduce synaptic plasticity and cognition, decreased Sir2alpha levels in the hippocampus and cerebral cortex, in proportion to an increase in protein oxidation. Vitamin E supplementation normalized, in the hippocampus and cerebral cortex, Sir2alpha levels that had been reduced by the high-fat diet. Neither the high-fat diet nor vitamin E supplementation affected cerebellar Sir2alpha. Vitamin E reduced, in the hippocampus, the oxidized nucleic acids that were increased by the high-fat diet. Western blot analysis showed higher contents of Sir2alpha in the hippocampus and cerebellum than in the cerebral cortex. Sir2alpha immunostaining was predominantly localized in the mossy fibre system and the dentate gyrus granule layer of the hippocampal formation. The high-fat diet decreased Sir2alpha immunostaining while vitamin E supplementation reversed these effects. Given that oxidative stress is a subproduct of dysfunctional energy homeostasis, we measured AMP-activated protein kinase (AMPK) to have an indication of the energy status of cells. Hippocampal levels of total and phosphorylated AMPK were reduced after high fat consumption and levels were normalized by vitamin E treatment. The present results show that oxidative stress and energy homeostasis associated with the consumption of the high-fat diet are critical for the regulation of Sir2alpha, with important implications for mechanisms of neural repair.
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PMID:Oxidative stress modulates Sir2alpha in rat hippocampus and cerebral cortex. 1681 60

Vitamin E succinate (VES), a potential cancer therapeutic agent, potently induces apoptosis and inhibits the growth of various cancer cells. Autophagy has been supposed to promote cancer cell survival or trigger cell death, depending on particular cancer types and tumor microenvironments. The role of autophagy in the growth suppressive effect of VES on gastric cancer cell is basically unknown. We aimed to determine whether and how autophagy affected the VES-induced inhibition of SGC-7901 human gastric carcinoma cell growth. SGC-7901 cells were treated with VES or pre-treated with autophagy inhibitor, chloroquine (CQ) and 3-methyladenine (3-MA). Electron microscopy, fluorescence microscopy and Western blot were used to study whether VES induced autophagy reaction in SGC-7901 cells. Western blot evaluated the activities of the mammalian target of rapamycin (mTOR) axis. Then we used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry to detect the level of cell viability and apoptosis. Collectively, our data indeed strongly support our hypothesis that VES treatment produced cytological variations that depict autophagy, increased the amount of intracellular green fluorescent protein-microtubule associated protein 1 light chain 3 (GFP-LC3) punctate fluorescence and the number of autophagic vacuoles. It altered the expression of endogenous autophagy marker LC3. VES activated the suppression of mTOR through inhibiting upstream regulators p38 MAPK and Akt. mTOR suppression consequently inhibited the activation of mTOR downstream targets p70S6K and 4E-BP-1. The activation of the upstream mTOR inhibitor AMPK had been up-regulated by VES. The results showed that pre-treatment SGC-7901 with autophagy inhibitors before VES treatment could increase the capacity of VES to reduce cell viability and to provoke apoptosis. In conclusion, VES-induced autophagy participates in SGC-7901 cell protection by inhibiting mTOR axis phosphorylation. Our findings not only strengthen our understanding of the roles of autophagy in cancer biology, but may also be useful for developing new treatments for gastric cancer patients.
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PMID:Protective Macroautophagy Is Involved in Vitamin E Succinate Effects on Human Gastric Carcinoma Cell Line SGC-7901 by Inhibiting mTOR Axis Phosphorylation. 2616 48