trans-Resveratrol Protects Ischemic PC12 Cells by Inhibiting the Hypoxia Associated Transcription Factors and Increasing the Levels of Antioxidant Defense Enzymes

• Published in: ACS chemical neuroscience Vol. 4; no. 2; pp. 285 - 294
• Main Authors: Agrawal, Megha, Kumar, Vivek, Singh, Abhishek K, Kashyap, Mahendra P, Khanna, Vinay K, Siddiqui, Maqsood A, Pant, Aditya B
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20-02-2013
• Subjects: Animals; Antioxidants - pharmacology; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - metabolism; Cell Death; Cell Hypoxia; HSP27 Heat-Shock Proteins - drug effects; HSP27 Heat-Shock Proteins - metabolism; Hypoxia - metabolism; Hypoxia-Inducible Factor 1, alpha Subunit - drug effects; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Ischemia - metabolism; L-Lactate Dehydrogenase - drug effects; L-Lactate Dehydrogenase - metabolism; PC12 Cells; Rats; Reactive Oxygen Species - metabolism; STAT3 Transcription Factor - drug effects; STAT3 Transcription Factor - metabolism; Stilbenes - pharmacology; Superoxide Dismutase - drug effects; Superoxide Dismutase - metabolism; Superoxide Dismutase-1; TRPM Cation Channels - drug effects; TRPM Cation Channels - metabolism; intracellular calcium; trans-resveratrol; OGD; PC12 cells; ROS
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/cn300143m

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 Ca2+ influx by upregulating native L-type Ca2+ channels and reactive oxygen species (ROS) generation. This reactive oxygen species generation and increase in intracellular Ca2+ 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 Ca2+ 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.