Involvement of oxidative stress and TRP channels in cerebral ischemia

Year 2019, Cilt 11 Supp 1 (BRS), 11 - 11, 21.06.2019

Hamit Hakan Armağan

https://doi.org/10.37212/jcnos.584688

Abstract

Abnormalities of intracellular free Ca+2 concentration is caused through activation of mitochondrial membrane depolarization by excessive levels of reactive oxygen species (ROS). In etiology of cerebral ischemia, the abnormalities of intracellular free Ca+2 concentration and excessive productions of ROS play an important role in the pathophysiology of cerebral ischemia (Chinopoulos and Adam-Vizi, 2006). Ca2+ influx occurs through activation of different cation channels. Well-known cations channels in cell membrane are chemical and voltage gated channels. Apart from the well-known cation channels, there is transient receptor potential (TRP) superfamily. The TRP superfamily is containing 28 members in 7 subfamilies in mammalian. Activation and inhibition mechanisms of the TRP channels are very different from the wellknown calcium channels. TRPM2 channel is activated by ADP-ribose NAD+. Another member of TRP superfamily is TRPV1 channel and it is activated several stimuli, including capsaicin, heat (≥43 °C) and acidic pH (≤ 6) (Chinopoulos and Adam-Vizi, 2006; Toda et al, 2019). Both channels are also activated by oxidative stress. Recent data indicated protective roles of some drugs on cerebral ischemia in rodents. One of the drug is duloxetine (DULOX) and it reduced the effects of Ca2+ entry and ROS through inhibition of TRPM2 channel (Toda et al. 2019). Another drug is dexmedetomidine (DEX) and it is an important drug for long-term sedation in intensive care patients, because it induces a rapid response. In addition to the intensive care patients, it has been started to use for sedation and analgesia in emergency medicine patients (McMorrow and Abramo, 2012). Recently, the protective role of DEX through inhibition of TRPM2 and TRPV1 channels on experimental cerebral ischemia in rats was reported (Akpınar et al. 2016). In the oral presentation, I discussed novel effects of TRPM2, TRPV1 and oxidative stress on the cerebral ischemia in rodents and human.  I concluded that the results of current data suggest that antioxidant drugs such as DEX and DULOX treatments reduce cerebral ischemia-induced oxidative stress and intracellular Ca2+ signaling through inhibition of TRPM2 and TRPV1 channels. It seems to that the exact relationship between TRP channel activation and the drugs in cerebral ischemia still remains to be determined. 

Keywords

Dexmedetomidine, Duloxetine, Cerebral Ischemia, Oxidative stress, TRPM2 channel, TRPV1 channel

References

• Akpınar H, Nazıroğlu M, Övey İS, Çiğ B, Akpınar O. 2016. The neuroprotective action of dexmedetomidine on apoptosis, calcium entry and oxidative stress in cerebral ischemia-induced rats: Contribution of TRPM2 and TRPV1 channels. Sci Rep. 6:37196.
• Chinopoulos C, Adam-Vizi V. 2006. Calcium, mitochondria and oxidative stress in neuronal pathology. Novel aspects of an enduring theme. FEBS J. 273(3):433-50.
• McMorrow SP, Abramo TJ. Dexmedetomidine sedation: uses in pediatric procedural sedation outside the operating room. Pediatr Emerg Care. 2012;28(3):292-296.
• Toda T, Yamamoto S, Umehara N, Mori Y, Wakamori M, Shimizu S. 2019. Protective effects of duloxetine against cerebral ischemia-reperfusion injury via transient receptor potential melastatin 2 inhibition. J Pharmacol Exp Ther. 368(2):246-254.