Research
| Title： | The contribution of TRPV1 channel to 20-HETE-Aggravated ischemic neuronal injury |
|---|---|
| First author： | Zhang, Xiaofan; El Demerdash, Nagat; Falck, John R.; Munnuri, Sailu; Koehler, Raymond C.; Yang, Zeng-Jin |
| Journal： | PROSTAGLANDINS & OTHER LIPID MEDIATORS |
| Years： | 2018 |
| DOI： | 10.1016/j.prostaglandins.2018.07.001 |
| Abstract： | 20-Hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P450 (CYP) 4A/4F-derived metabolite of arachidonic acid, directly contributes to ischemic neuronal injury. However, little is known about mediators of 20-HETE neurotoxicity after ischemia. Here, we focus on the role of transient receptor potential cation channel subfamily V member 1 (TRPV1) in 20-HETE-induced neurotoxicity. Our results showed that TRPV1 and CYP4A irnmunoreactivity were colocalized in neurons. TRPV1 inhibition attenuated 20-HETE mimetic 20-5,14-HEDGE-induced reactive oxygen species (ROS) production and neuronal injury in cultured neurons and protected ischemic neurons in vitro and in vivo. TRPV1 inhibition in combination with 20-HETE synthesis inhibitor HET0016 did not produce additional protective effects. Furthermore, TRPV1 genetic inhibition and NADPH oxidase inhibitor gp9lds-dat each attenuated ROS production to a similar extent. However, combined treatment did not achieve additional reduction. Therefore, we conclude that TRPV1 channels are involved in 20-HETE's ROS generation and neurotoxicity after ischemia. |
