The contribution of TRPV1 channel to 20-HETE—Aggravated ischemic neuronal injury

Xiaofan Zhang, Nagat El Demerdash, John R. Falck, Sailu Munnuri, Raymond C Koehler, Zeng Jin Yang

Research output: Contribution to journalReview article

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 languageEnglish (US)
Pages (from-to)63-68
Number of pages6
JournalProstaglandins and Other Lipid Mediators
Volume137
DOIs
StatePublished - Jul 1 2018

Fingerprint

Wounds and Injuries
Neurons
Reactive Oxygen Species
Ischemia
Cytochrome P-450 CYP4A
Transient Receptor Potential Channels
NADPH Oxidase
Metabolites
Arachidonic Acid
Cytochrome P-450 Enzyme System
20-hydroxy-5,8,11,14-eicosatetraenoic acid

Keywords

  • 20-HETE
  • Hypoxic-ischemic injury
  • Neonatal
  • Oxygen–glucose deprivation
  • TRPV1

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

Cite this

The contribution of TRPV1 channel to 20-HETE—Aggravated ischemic neuronal injury. / Zhang, Xiaofan; El Demerdash, Nagat; Falck, John R.; Munnuri, Sailu; Koehler, Raymond C; Yang, Zeng Jin.

In: Prostaglandins and Other Lipid Mediators, Vol. 137, 01.07.2018, p. 63-68.

Research output: Contribution to journalReview article

Zhang, Xiaofan ; El Demerdash, Nagat ; Falck, John R. ; Munnuri, Sailu ; Koehler, Raymond C ; Yang, Zeng Jin. / The contribution of TRPV1 channel to 20-HETE—Aggravated ischemic neuronal injury. In: Prostaglandins and Other Lipid Mediators. 2018 ; Vol. 137. pp. 63-68.
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