Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cu/Zn superoxide dismutase (SOD1) is a key antioxidant enzyme. Deficiency of SOD1 is associated with various human diseases, including cancer. Here, we report that SOD1 is succinylated and that succinylation decreases its activity. SIRT5 binds to, desuccinylates and activates SOD1. SOD1-mediated ROS reduction is increased when SIRT5 is co-expressed. Furthermore, mutation of the SOD1 succinylation site inhibits the growth of lung tumor cells. These results reveal a novel post-translational regulation of SOD1 by means of succinylation and SIRT5-dependent desuccinylation, which is important for the growth of lung tumor cells.
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PMID:SIRT5 desuccinylates and activates SOD1 to eliminate ROS. 2414 62

Parkinson's disease (PD) is characterized by progressive loss of nigrostriatal dopaminergic neurons that results in motor deficits including resting tremor, rigidity, bradykinesia, and postural instability. Despite decades of intensive study, the underlying molecular mechanisms are not fully understood. Multiple lines of evidence indicate that mitochondrial dysfunction and oxidative stress contribute to neuronal death, which is the key feature of neurodegeneration. Mitochondria are pivotal organelles that host essential functions in neuronal viability including energy production, oxidative phosphorylation, calcium buffering, redox homeostasis and apoptosis. SIRT5, which localizes in the mitochondrial matrix, is nicotinamide adenine dinucleotide (NAD(+))-dependent histone deacetylase. The physiological and pathophysiological functions of SIRT5 in vivo remain elusive although it is known to be an important energy sensor. Here, we investigated the role of SIRT5 in the pathogenesis of PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We present evidence that SIRT5 deficiency, by itself, does not affect motor and non-motor functions; however, lack of SIRT5 exacerbates MPTP-induced motor deficits. Consistently, MPTP-exposed SIRT5 knockout mice exhibited more severe nigrostriatal dopaminergic degeneration than that observed in wild-type controls. Furthermore, deletion of SIRT5 leads to a larger decrease, relative to control, in the expression level of manganese superoxide dismutase (SOD2), a mitochondria-specific antioxidant enzyme, after MPTP induction. These findings indicate that SIRT5 ameliorates MPTP-induced nigrostriatal dopaminergic degeneration via preserving mitochondrial antioxidant capacity.
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PMID:Protective role of SIRT5 against motor deficit and dopaminergic degeneration in MPTP-induced mice model of Parkinson's disease. 2554 Oct 39