Selenium prevents interferon-gamma induced activation of TRPM2 channel and inhibits inflammation, mitochondrial oxidativ
- PDF / 2,369,481 Bytes
- 14 Pages / 595.276 x 790.866 pts Page_size
- 23 Downloads / 151 Views
ORIGINAL ARTICLE
Selenium prevents interferon-gamma induced activation of TRPM2 channel and inhibits inflammation, mitochondrial oxidative stress, and apoptosis in microglia Yener Akyuva 1 & Mustafa Nazıroğlu 2,3,4 & Kenan Yıldızhan 2 Received: 29 July 2020 / Accepted: 22 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Microglia as the primary immune cells of brain act protective effects against injuries and infections in the central nervous system. Inflammation via excessive Ca2+ influx and oxygen radical species (ROS) generation is a known factor in many neurodegenerative disorders. Importantly, the Ca2+ permeable TRPM2 channel is activated by oxidative stress. Thus, TRPM2 could provide the excessive Ca2+ influx in the microglia. Although TRPM2 expression level is high in inflammatory cells, the interplay between mouse microglia and TRPM2 channel during inflammation is not fully identified. Thus, it is important to understand the mechanisms and factors involved in order to enhance neuronal regeneration and repair. The data presented here indicate that TRPM2 channels were activated in microglia cells by interferon-gamma (IFNγ). The IFNγ treatment further increased apoptosis (early and late) and cytokine productions (TNF-α, IL-1β, and IL-6) which were due to increased lipid peroxidation and ROS generations as well as increased activations of caspase −3 (Casp-3) and − 9 (Casp-9). However, selenium treatment diminished activations of TRPM2, cytokine, Casp-3, and Casp-9, and levels of lipid peroxidation and mitochondrial ROS production in the microglia that were treated with IFNγ. Moreover, addition of either PARP1 inhibitors (PJ34 or DPQ) or TRPM2 blockers (2APB or ACA) potentiated the modulator effects of selenium. These results clearly suggest that IFNγ leads to TRPM2 activation in microglia cells; whereas, selenium prevents IFNγ-mediated TRPM2 activation and cytokine generation. Together the interplay between IFNγ released from microglia cells is importance in brain inflammation and may affect oxidative cytotoxicity in the microglia. Keywords Apoptosis . Inflammation . Microglia . Mitochondria . TRPM2 channel
Introduction Microglia are the primary immune cells that protect against injuries and infections in the central nervous system (CNS) (Neumann 2001). There are two major phenotypes of the
* Mustafa Nazıroğlu [email protected] 1
Departmant of Neurosurgery, Faculty of Medicine, Hatay Mustafa Kemal University, Hatay, Turkey
2
Department of Biophysics, Faculty of Medicine, Suleyman Demirel University, Isparta, Turkey
3
Drug Discovery Unit, BSN Health, Analysis and Innovation Ltd. Inc. Teknokent, Isparta, Turkey
4
Neuroscience Research Center (NÖROBAM), Suleyman Demirel University, TR-32260 Isparta, Turkey
microglia as the non-activated and activated form in neuronal tissues. Non-activated microglial cell function as network and stays in contact with surrounding neurons (Kierdorf and Prinz 2013). In the presence of a stimulator, the non-activated fo
Data Loading...
