Glutathione Depletion and Parkinsonian Neurotoxin MPP+-Induced TRPM2 Channel Activation Play Central Roles in Oxidative Cytotoxicity and Inflammation in Microglia.

Molecular Neurobiology
Kenan Yıldızhan, Mustafa Nazıroğlu

Abstract

Parkinson's disease (PD) is one of most common neurodegenerative diseases. Environmental stressors such as oxidative stress (OS), calcium ion influx, apoptosis, and inflammation mechanisms are linked to activated microglia in patients with PD. The OS-dependent activated transient receptor potential melastatin 2 (TRPM2) channel is modulated in several neurons by glutathione (GSH). However, the cellular and molecular effects of GSH alteration on TRPM2 activation, OS, apoptosis, and inflammation in the microglia remain elusive. The microglia of TRPM2 wild-type (TRPM2-WT) and knockout (TRPM2-KO) mice were divided into control, PD model (MPP), L-buthionine sulfoximine (BSO), MPP + BSO and MPP + BSO + GSH groups. MPP-induced increases in apoptosis, death, OS, lipid peroxidation, PARP1, caspase-3 and caspase-9, inflammatory cytokines (IL-1β, TNF-α, IL-6), and intracellular free Zn2+ and Ca2+ levels in the microglia of TRPM2-WT mice were further increased by the BSO treatment, although they were diminished by the GSH treatment. Their levels were further reduced by PARP1 inhibitors (PJ34 and DPQ) and TRPM2 blockers (ACA and 2-APB). However, the effects of MPP and BSO were not observed in the microglia of TRPM2-KO mice. Taken together, o...Continue Reading

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Citations

Dec 15, 2020·Chemico-biological Interactions·Hamit Hakan Armağan, Mustafa Nazıroğlu
Feb 6, 2021·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Dilek Özkaya, Mustafa Nazıroğlu
Dec 16, 2020·Antioxidants·Muhammad Syahreel Azhad Sha'fieSharifah Alawieyah Syed Mortadza
Jun 15, 2021·Frontiers in Neuroscience·Eduard YakubovHans-Herbert Steiner
Aug 10, 2021·Molecular Neurobiology·Yener Yazğan, Mustafa Nazıroğlu
Sep 30, 2021·Journal of Receptor and Signal Transduction Research·Kenan Yıldızhan, Mustafa Nazıroğlu
Jan 7, 2022·Metabolic Brain Disease·Mustafa Nazıroğlu

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Methods Mentioned

BETA
environmental stress
ELISA
Fluorescence
Assay
MDA
imaging technique

Software Mentioned

ZEN
ImageJ
Imaris
SPSS
Carry Eclipse

Related Concepts

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis