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 immunoreactivity 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 gp91ds-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.
Original language | English (US) |
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Pages (from-to) | 63-68 |
Number of pages | 6 |
Journal | Prostaglandins and Other Lipid Mediators |
Volume | 137 |
DOIs | |
State | Published - Jul 2018 |
Keywords
- 20-HETE
- Hypoxic-ischemic injury
- Neonatal
- Oxygen–glucose deprivation
- TRPV1
ASJC Scopus subject areas
- Biochemistry
- Physiology
- Pharmacology
- Cell Biology