Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

Table 1

List of confirmed nitrated hepatic proteins and functional consequences.

Nitrated proteins	Activity	Hepatic indication (observed or expected)	References
Carbamoyl phosphate synthase-1 (CPS-1)	Decrease	Hyperammonemia, hepatic encephalopathy	[33]
Glutamine synthetase (GS)	Decrease	Hyperammonemia, hepatic encephalopathy related to sepsis	[34]
3-Ketoacyl-CoA thiolase (Thiolase)	Decrease	Decreased β-oxidation of fatty acids with increased hepatic steatosis	[35]
Aldehyde dehydrogenase 2 (ALDH2)	Decrease	Accumulation of acetaldehyde and lipid peroxides with increased aldehyde-related liver toxicity	[35]
Complex I (NADH ubiquinone oxidoreductase)	Decrease	ROS leakage, contributing to decreased energy production and increased apoptosis or necrosis	[36]
Complex V (ATP synthase)	Decrease	Decreased energy production with increased sensitivity toward necrotic liver injury	[11, 35–38]
Cytochrome p450 2E1, B6; (CYP2E1, CYP2B6)	Decrease	Drug metabolism: ROS production and ethanol- and drug-induced liver toxicity	[39]
Cytosolic Cu/Zn-SOD (SOD1)	Decrease	Decreased antioxidant defense with increased drug- or toxin-mediated hepatic damage	[35, 40]
Mitochondrial Mn-SOD (SOD2)	Decrease	Same as above	[35, 41]
Glutathione peroxidase (GPX)	Decrease	Same as above	[35]
Glutathione reductase (GR)	Decrease	Increased oxidative stress with elevated levels of oxidized glutathione	[42, 43]
AKT, IRβ, IRS-1, IRS-2	Decrease	Decrease insulin signaling with increased hepatic insulin resistance and fatty liver	[44]
CD95	Decrease	Increased hepatic anti-inflammatory defense	[45]
List of nitrated mitochondrial and cytosolic proteins	Not confirmed*	Not confirmed but likely contributing to mitochondrial dysfunction, ER stress, and liver damage	[35]
List of nitrated mitochondrial proteins	Not confirmed	Not confirmed but likely contributing to mitochondrial dysfunction and liver damage	[46]
List of nitrated proteins in different compartments	Not confirmed	Not confirmed but likely contributing to mitochondrial dysfunction, ER stress, and liver damage	[47]
Glutathione-S-transferase (GST)	Increase	Increased hepatic antioxidant defense	[41]
Heat shock protein 90 (Hsp90)**	Increase	Conversion to a toxic protein, contributing to increased liver toxicity	[48]
Protein phosphatase type 2A (PP2A)**	Increase	Increased microvascular endothelial permeability	[49]

∗With the exception of the five proteins characterized in detail, as in the reference [35].
∗∗Not confirmed in liver, but expected to occur.