Pannexin hemichannels: A novel promising therapy target for oxidative stress related diseases

Abstract

Pannexins, which contain three subtypes: pannexin-1, -2, and -3, are vertebrate glycoproteins that form non-junctional plasma membrane intracellular hemichannels via oligomerization. Oxidative stress refers to an imbalance of the generation and elimination of reactive oxygen species (ROS). Studies have shown that elevated ROS levels are pivotal in the development of a variety of diseases. Recent studies indicate that the occurrence of these oxidative stress related diseases is associated with pannexin hemichannels. It is also reported that pannexins regulate the production of ROS which in turn may increase the opening of pannexin hemichannels. In this paper, we review recent researches about the important role of pannexin hemichannels in oxidative stress related diseases. Thus, pannexin hemichannels, novel therapeutic targets, hold promise in managing oxidative stress related diseases such as the tumor, inflammatory bowel diseases (IBD), pulmonary fibrosis, chronic obstructive pulmonary disease (COPD), cardiovascular disease, insulin resistance (IR), and neural degeneration diseases.

The Potential of Lactobacillus spp. for Modulating Oxidative Stress in the Gastrointestinal Tract

“…In addition to NOXs, mitochondria are another major intracellular source of ROS, which produce ROS primarily through electron leakage from Complex I (NADH dehydrogenase) as well as Complex III (ubiquinol–cytochrome c oxidoreductase), namely, two discrete points in the electron transporting chain [ 29 , 30 ]. Apart from the above, other endogenous sources of ROS are enzymes including xanthine oxidoreductase (XOR), cytochrome P450 family (CYPs), cyclooxygenase (COX) and lipoxygenase (LOX), as well as a few peroxisomal oxidases [ 31 , 32 ]. The ROS level normally remains very low inside the cells as a result of the well-developed antioxidant systems in eukaryotes, which can be classified as two categories, including ROS scavenging enzymes such as superoxide dismutase (SOD) and catalase, as well as non-enzymatic antioxidants like glutathione (GSH) and flavonoids [ 33 ].…”

Mitochondrial Dysfunction as Substrate for Arrhythmogenic Cardiomyopathy: A Search for New Disease Mechanisms

“…Besides Cx43 hemichannels, pannexin-1 channels are also involved in cardiac fibrosis formation, likely via release of ATP from the cardiomyocytes (Nishida et al, 2008;Kar et al, 2012;Li et al, 2015). Pannexin-1 can be activated by Ca 2+ released from the SR and allow passage of Ca 2+ , ATP and other small molecules across the membrane, in a manner similar to that of Cx43 hemichannels (Figure 3) (Li et al, 2015;Xu et al, 2018). Oxidative stress activates Pannexin-1 hemichannels and does increase ATP release of cardiomyocytes via Pannexin-1 (Zhang et al, 2008;Dolmatova et al, 2012).…”

“…Oxidative stress activates Pannexin-1 hemichannels and does increase ATP release of cardiomyocytes via Pannexin-1 (Zhang et al, 2008;Dolmatova et al, 2012). Pannexin-1 mediated ATP release activates G-coupled P2X and P2Y receptors, further triggering the accumulation of ROS, via their underlying pathways (Figure 3) (Onami et al, 2014;Díaz-Vegas et al, 2015;Xu et al, 2018). P2X and P2Y activation enhances the transcription of fibrotic genes such as TGF-β1 (Nishida et al, 2008).…”

Trimetallic Nitride Endohedral Fullerenes Carboxyl-Gd3N@C80: A New Theranostic Agent for Combating Oxidative Stress and Resolving Inflammation

“…22 To confirm our cell-free EPR assays on radical scavenging, an in vitro macrophage cell model (Raw 264.7 cells with or without LPS stimulation) was adopted for biological characterization. First of all, we observed little cytotoxicity of all three nanoparticles at 0.1, 1, and 10 µ M concentration for up to 24 h with or without LPS treatment (Figures S1 S2).…”