Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress plays crucial role in the pathogenesis of neurodegenerative diseases. However, the precise mechanism for an increased production of reactive oxygen species (ROS) under pathological conditions is not yet fully understood. We have recently demonstrated an implication of phosphatase and tensin homologue deleted on chromosome 10 (PTEN), a tumor suppressor, in ROS generation and neuronal apoptosis induced by staurosporine. These findings raised further interest whether PTEN functions as a common mediator of oxidative stress in neurodegenerative processes. To address this issue, neural cells were exposed to oxygen-glucose deprivation (OGD) and to the neurotoxin 1-methyl-4-phenylpyridinium iodide (MPP(+)), which mimic cerebral ischemia and Parkinson's disease, respectively. OGD for 4 h followed by 16 h of reoxygenation or incubation with MPP(+) (250 microM) for 48 h induced 33% and 45% neuronal death in rat hippocampal and in human dopaminergic SH-SY5Y neurons, respectively, accompanied by a gradual increase in the intracellular level of ROS. The increase in ROS by OGD and by MPP(+) did not cause oxidative inactivation of PTEN and thus, PTEN remains constitutively active. In support, the protein level of PTEN was not reduced in both cell cultures after challenging with OGD or MPP(+). Importantly, the elevated intracellular ROS levels and the neuronal death caused by OGD or by MPP(+) toxicity were significantly inhibited when PTEN was downregulated by a specific antisense oligonucleotide or by siRNA. Because SOD2 protein level is not altered either by knockdown of PTEN nor by an inhibition of the PI3K/Akt signalling, we suggest that SOD2 do not contribute to the pathomechanism of oxidative stress induced by PTEN or by inhibiting the related Akt signalling. The present study highlights PTEN as a crucial and common mediator of ROS generation and neuronal death and suggests that PTEN could become a potential therapeutic target for interfering with neurodegeneration.
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PMID:Implication of PTEN in production of reactive oxygen species and neuronal death in in vitro models of stroke and Parkinson's disease. 1716 62

Trans sodium crocetinate (TSC) has been reported to exert a protective effect against cerebral ischemia/reperfusion (I/R) injury. However, whether TSC protects against myocardial ischemia/reperfusion (MI/R) injury remains unknown. Herein, we found that TSC treatment reduced myocardial infract size and elevated serum LDH and CK activities of MI/R rats. TSC administration attenuated oxidative stress in MI/R rats and H9C2 cells exposed to oxygen glucose deprivation/reperfusion (OGD/R). TSC administration relieved I/R-induced myocardial apoptosis in vivo and in vitro, as evidenced by reduced number of TUNEL positive cells, accompanying with marked decreases in caspase-3 activity and Bax protein level and an increase in Bcl-2 protein level. TSC treatment markedly increased SIRT3 activity and SIRT3 and SOD2 protein levels, and could also diminished the phosphorylation of FOXO3a protein. Additionally, TSC treatment attenuated the acetylation of FOXO3a and SOD2 protein. But, these effects were obviously blocked by SIRT3 knockdown. Besides, SIRT3 knockdown blocked the cardioprotective effect of TSC on OGD/R-induced oxidative stress, apoptosis and mitochondrial dysfunction in vitro. In summary, TSC alleviates I/R-induced myocardial oxidative stress and apoptosis via the SIRT3/FOXO3a/SOD2 signaling pathway. Our study suggests that TSC may become a novel drug for the treatment of MI/R injury.
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PMID:Trans sodium crocetinate alleviates ischemia/reperfusion-induced myocardial oxidative stress and apoptosis via the SIRT3/FOXO3a/SOD2 signaling pathway. 3095