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

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

doi:10.1016/j.prostaglandins.2018.07.001

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

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

Biochemistry

Research output: Contribution to journal › Review article › peer-review

8 Scopus citations

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)
Pages (from-to)	63-68
Number of pages	6
Journal	Prostaglandins and Other Lipid Mediators
Volume	137
DOIs	https://doi.org/10.1016/j.prostaglandins.2018.07.001
State	Published - Jul 2018

Keywords

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

ASJC Scopus subject areas

Biochemistry
Physiology
Pharmacology
Cell Biology

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10.1016/j.prostaglandins.2018.07.001

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title = "The contribution of TRPV1 channel to 20-HETE—Aggravated ischemic neuronal injury",

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.",

keywords = "20-HETE, Hypoxic-ischemic injury, Neonatal, Oxygen–glucose deprivation, TRPV1",

author = "Xiaofan Zhang and {El Demerdash}, Nagat and Falck, {J R} and Sailu Munnuri and Koehler, {Raymond C.} and Yang, {Zeng Jin}",

note = "Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2018",

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doi = "10.1016/j.prostaglandins.2018.07.001",

language = "English (US)",

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T1 - The contribution of TRPV1 channel to 20-HETE—Aggravated ischemic neuronal injury

AU - Zhang, Xiaofan

AU - El Demerdash, Nagat

AU - Falck, J R

AU - Munnuri, Sailu

AU - Koehler, Raymond C.

AU - Yang, Zeng Jin

PY - 2018/7

Y1 - 2018/7

N2 - 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.

AB - 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.

KW - 20-HETE

KW - Hypoxic-ischemic injury

KW - Neonatal

KW - Oxygen–glucose deprivation

KW - TRPV1

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

Abstract

Keywords

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