Arachidonic Acid Induces ARE/Nrf2-Dependent Heme Oxygenase-1 Transcription in Rat Brain Astrocytes

Molecular Neurobiology
Chih-Chung LinChuen-Mao Yang

Abstract

Arachidonic acid (AA) is a major product of phospholipid hydrolysis catalyzed by phospholipase A2 during neurodegenerative diseases. AA exerts as a second messenger to regulate various signaling components which may be involved in different pathophysiological processes. Astrocytes are the main types of CNS resident cells which maintain and support the physiological function of brain. AA has been shown to induce ROS generation through activation of NADPH oxidases (Noxs) which may play a key role in the expression of heme oxygenase-1 (HO-1). Therefore, this study was designed to investigate the mechanisms underlying AA-induced HO-1 expression in rat brain astrocytes (RBA-1). We found that AA induced HO-1 protein and mRNA expression and promoter activity in RBA-1, which was mediated through the synthesis of 15-deoxy-Δ12,14-prostaglandin D2-activated peroxisome proliferator-activated receptor-γ (PPARγ) receptors. This note was confirmed by transfection with PPARγ small interfering RNAs (siRNA) which attenuated the AA-mediated responses. AA-induced HO-1 expression was mediated through Nox/ROS generation, which was inhibited by Nox inhibitors (diphenyleneiodonium and apocynin) and ROS scavengers (N-acetyl cysteine). Moreover, AA-indu...Continue Reading

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Citations

Mar 31, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Jan KorbeckiMieczysław Dutka
Sep 26, 2020·International Journal of Molecular Sciences·Shiri LiHirohito Ichii
Dec 15, 2020·Pharmacology & Therapeutics·Jaana van GastelStuart Maudsley
Aug 18, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Merilin Al Sharif
Sep 16, 2021·Journal of Mass Spectrometry : JMS·Junjie ZhangChun Cai

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Methods Mentioned

BETA
protein assay
transfections
PCR
transfection
Immunoprecipitation
Assay
ChIP
ELISA
nuclear translocation

Software Mentioned

SCAN
UN
GraphPad Prism
IT

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