title: trans-Resveratrol protects ischemic PC12 Cells by inhibiting the hypoxia associated transcription factors and increasing the levels of antioxidant defense enzymes.
abstract: An in vitro model of ischemic cerebral stroke [oxygen-glucose deprivation (OGD) for 6 h followed by 24 h reoxygenation (R)] with PC12 cells increases Ca(2+) influx by upregulating native L-type Ca(2+) channels and reactive oxygen species (ROS) generation. This reactive oxygen species generation and increase in intracellular Ca(2+) triggers the expression of hypoxic homeostasis transcription factors such as hypoxia induced factor-1 alpha (HIF-1α), Cav-beta 3 (Cav β3), signal transducer and activator of transcription 3 (STAT3), heat shock protein 27 (hsp-27), and cationic channel transient receptor potential melastatin 7 (TRPM7). OGD insulted PC12 cells were subjected to biologically safe doses (5, 10, and 25 μM) of trans-resveratrol in three different treatment groups: 24 h prior to OGD (pre-treatment); 24 h post OGD (post-treatment); and from 24 h before OGD to end of reoxygenation period (whole-treatment). Here, we demonstrated that OGD-R-induced neuronal injury/death is by reactive oxygen species generation, increase in intracellular calcium levels, and decrease in antioxidant defense enzymes. trans-Resveratrol increases the viability of OGD-R insulted PC12 cells, which was assessed by using MTT, NRU, and LDH release assay. In addition, trans-resveratrol significantly decreases reactive oxygen species generation, intracellular Ca(2+) levels, and hypoxia associated transcription factors and also increases the level of antioxidant defense enzymes. Our data shows that the whole-treatment group of trans-resveratrol is most efficient in decreasing hypoxia induced cell death through its antioxidant properties.
authors: CSIR-Indian Institute of Toxicology Research, Lucknow, India.
authors: Megha
authors: M
authors: Agrawal
authors: Vivek
authors: V
authors: Kumar
authors: Abhishek K
authors: AK
authors: Singh
authors: Mahendra P
authors: MP
authors: Kashyap
authors: Vinay K
authors: VK
authors: Khanna
authors: Maqsood A
authors: MA
authors: Siddiqui
authors: Aditya B
authors: AB
authors: Pant
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death; D015687:Cell Hypoxia; D055551:HSP27 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D050796:STAT3 Transcription Factor / Q000187:drug effects / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D050053:TRPM Cation Channels / Q000187:drug effects / Q000378:metabolism
chemical_list: D000975:Antioxidants; C484333:Cacnb3 protein, rat; D015220:Calcium Channels; D055551:HSP27 Heat-Shock Proteins; C497444:Hif1a protein, rat; C486114:Hspb1 protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D013267:Stilbenes; D050053:TRPM Cation Channels; D007770:L-Lactate Dehydrogenase; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; C486584:Trpm7 protein, rat; D000077185:Resveratrol; D002118:Calcium