Alpha lipoic acid attenuates hypoxia-induced apoptosis, inflammation and mitochondrial oxidative stress via inhibition of TRPA1 channel in human glioblastoma cell line.
Apoptosis, overload Ca2+ entry and oxidative stress are induced in neurons by hypoxia. Drug-resistant cancer cells are killed by hypoxic conditions. α-Lipoic acid (ALA) has antioxidant and pro-oxidant functions. The TRPA1 channel is activated by oxidative stress and pro-oxidant ALA may have a regulator role in the TRPA1 activity in the human glioblastoma (DBTRG) cells. The aim of this study was to evaluate if a combination therapy of ALA with a hypoxia can alter the effect of this hypoxia through TRPA1 activation in the DBTRG cells. The DBTRG cells were divided into four treatment groups as control, ALA (50 μM), and hypoxia and hypoxia + ALA. Hypoxia in the cells was induced by CoCl2 (200 μM). Apoptosis, Annexin V, mitochondrial membrane depolarization (JC-1), reactive oxygen species (ROS) production, IL-1β, IL-18, caspase 3 and 9 values were increased through activation of TRPA1 (cinnamaldehyde) in the cells by the hypoxia induction, although cell viability, reduced glutathione and glutathione peroxidase values were decreased by the treatments. The values were modulated in the cells by TRPA1 blocker (AP18) and ALA treatments. Involvements of TRPA1 activity on values in the cells were also confirmed by patch-clamp and laser confocal microscopy analyses. In conclusion, apoptotic, inflammatory and oxidant effects of hypoxia were increased by activation of TRPA1, but its action on the values was decreased by the ALA treatment. ALA treatment could be used as an effective strategy in the treatment of hypoxia-induced oxidative stress, apoptosis and inflammation in the neurons.
['Deveci|Haci Ahmet|HA|', 'Akyuva|Yener|Y|', 'Nur|Gökhan|G|', 'Nazıroğlu|Mustafa|M|']
D000975:Antioxidants D017209:Apoptosis D045744:Cell Line, Tumor D002470:Cell Survival D005909:Glioblastoma D006801:Humans D007249:Inflammation D018836:Inflammation Mediators D008928:Mitochondria D018384:Oxidative Stress D017382:Reactive Oxygen Species D000074025:TRPA1 Cation Channel D008063:Thioctic Acid D000072258:Tumor Hypoxia
Apoptosis Inflammation TRPA1 Glioblastoma cells Hypoxia α-Lipoic acid