Ion Channels and Oxidative Stress as a Potential Link for the Diagnosis or Treatment of Liver Diseases

Abstract

Oxidative stress results from a disturbed balance between oxidation and antioxidant systems. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) may be either harmful or beneficial to the cells. Ion channels are transmembrane proteins that participate in a large variety of cellular functions and have been implicated in the development of a variety of diseases. A significant amount of the available drugs in the market targets ion channels. These proteins have sulfhydryl groups of cysteine and methionine residues in their structure that can be targeted by ROS and RNS altering channel function including gating and conducting properties, as well as the corresponding signaling pathways associated. The regulation of ion channels by ROS has been suggested to be associated with some pathological conditions including liver diseases. This review focuses on understanding the role and the potential association of ion channels and oxidative stress in liver diseases including fibrosis, alcoholic liver disease, and cancer. The potential association between ion channels and oxidative stress conditions could be used to develop new treatments for major liver diseases.

Acetaminophen‐induced liver injury is mediated by the ion channel TRPV4

“…Previous reports suggested that TRPV4 is expressed in both hepatoma cell lines and primary hepatocytes (16)(17)(18)(19). Indeed, by performing RT-PCR on Huh7, HepG2, and PHH cells as well as PMHs, we could confirm an expression of TRPV4 in these cells (Supplemental Fig.…”

“…The ion channel TRP vanilloid 4 (TRPV4) is expressed in several tissues and is involved in diverse physiologic functions by sensing osmolarity, pressure, and heat but also reactive oxygen species (ROS) (14,15). Other than that TRPV4 was shown to be expressed in both hepatoma cell lines and native hepatocytes, little is known about the role of TRPV4 in the liver (16)(17)(18)(19). However, TRPV4 mediates ROS-induced cell damage associated with ischemia and reperfusion in both cardiomyocytes and in the CNS (20)(21)(22)(23).…”

Oxidative stress in patients with refractory temporal lobe epilepsy and mesial temporal sclerosis: Possible association with major depressive disorder?

“…Studies have shown that OS could be associated with neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, pathologies involving chronic inflammations with consequent higher levels of OS due to an increase of ROS and RNS production [23][24][25][26]. In this context, OS markers have received substantial attention in recent years and many of them have been studied, such as MDA and TEAC [27].…”

TRP Channels as Emerging Therapeutic Targets for Neurodegenerative Diseases

“…However, the target proteins are retained in their oxidized forms and are activated as long as the antioxidant activity is reduced. To date, several studies have shown that oxidative stress is involved in the modulation of activities of voltage-gated Ca 2+ (Gorlach et al, 2015;Ramirez et al, 2016), Na + , and K + (Sesti et al, 2010) channels and ligandgated receptors such as NMDA (Kamat et al, 2016), AMPA (Joshi et al, 2015), GABA (Bradley and Steinert, 2016), and RyR (Zima and Mazurek, 2016). However, there is limited evidence that directly identifies the oxidative modification of a channel protein based on molecular mechanisms.…”