title: Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia.
abstract: BACKGROUND
  Mitochondrial dysfunction is one of the major events responsible for activation of neuronal cell death pathways during cerebral ischemia. Trace element selenium has been shown to protect neurons in various diseases conditions. Present study is conducted to demonstrate that selenium preserves mitochondrial functional performance, activates mitochondrial biogenesis and prevents hypoxic/ischemic cell damage.
  
  
  RESULTS
  The study conducted on HT22 cells exposed to glutamate or hypoxia and mice subjected to 60-min focal cerebral ischemia revealed that selenium (100 nM) pretreatment (24 h) significantly attenuated cell death induced by either glutamate toxicity or hypoxia. The protective effects were associated with reduction of glutamate and hypoxia-induced ROS production and alleviation of hypoxia-induced suppression of mitochondrial respiratory complex activities. The animal studies demonstrated that selenite pretreatment (0.2 mg/kg i.p. once a day for 7 days) ameliorated cerebral infarct volume and reduced DNA oxidation. Furthermore, selenite increased protein levels of peroxisome proliferator-activated receptor-γ coactivator 1alpha (PGC-1α) and nuclear respiratory factor 1 (NRF1), two key nuclear factors that regulate mitochondrial biogenesis. Finally, selenite normalized the ischemia-induced activation of Beclin 1 and microtubule-associated protein 1 light chain 3-II (LC3-II), markers for autophagy.
  
  
  CONCLUSIONS
  These results suggest that selenium protects neurons against hypoxic/ischemic damage by reducing oxidative stress, restoring mitochondrial functional activities and stimulating mitochondrial biogenesis.
authors: Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise (BRITE), North Carolina Central University, BRITE Building 2025, 302 East Lawson Street, Durham, NC 27707, USA.
authors: Suresh L
authors: SL
authors: Mehta
authors: Santosh
authors: S
authors: Kumari
authors: Natalia
authors: N
authors: Mendelev
authors: P Andy
authors: PA
authors: Li
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D020520:Brain Infarction / Q000209:etiology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000150:complications; D016923:Cell Death / Q000187:drug effects; D002461:Cell Line, Transformed; D004249:DNA Damage / Q000187:drug effects; D004195:Disease Models, Animal; D005452:Fluoresceins; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000633:toxicity; D006657:Histones / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008868:Microtubule Proteins / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D063269:Mitochondrial Turnover / Q000187:drug effects*; D009097:Multienzyme Complexes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009930:Organic Chemicals; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D017382:Reactive Oxygen Species / Q000378:metabolism; D012643:Selenium / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D005452:Fluoresceins; D006657:Histones; D008868:Microtubule Proteins; D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; D009930:Organic Chemicals; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D017382:Reactive Oxygen Species; D015534:Trans-Activators; D014157:Transcription Factors; C435731:fluoro jade; D018698:Glutamic Acid; D012643:Selenium