Depletion of Tip60/Kat5 affects the hepatic antioxidant system in mice.
Enver Fehim KocpinarNurdan Gonul BaltaciEbru AkkemikHarun BudakPublished in: Journal of cellular biochemistry (2022)
Tat-interactive protein 60 kDa (TIP60, also known as lysine acetyltransferase 5 [KAT5]) is a member of the MYST protein family with histone acetyltransferase activity. Recent studies have reported that TIP60 has multiple functions in many signal transduction mechanisms, especially p53-mediated apoptosis. Although the activation of apoptosis signaling pathways requires the presence of cellular reactive oxygen species (ROS) at a certain level, an imbalance between the production and consumption of ROS in cells results in oxidative stress (OS). In this study, we investigated for the first time how the absence of the Tip60 gene in the liver affects gene expression, enzyme activity, and protein expression of the hepatic antioxidant members localized in the cytoplasm, including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione S-transferase (GST). First, we successfully generated liver-specific Tip60 knockout mice (mutants) using Cre/LoxP recombination. The reduced glutathione level and nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) expression, a marker of OS, increased significantly in the Tip60 mutant liver. Gene expression, activity, and protein expression of the enzymatic antioxidant system, including SOD, CAT, GR, GPx, and GST were investigated in mutants and control groups. Despite a significant correlation between the gene, enzyme activity, and protein content for CAT and GR, this was not true for SOD and GPx. The overall results suggest that TIP60 acts on the hepatic antioxidant system both at the gene and protein levels, but the actual effect of the deletion of Tip60 is observed at the protein level, especially for SOD and GPx.
Keyphrases
- oxidative stress
- gene expression
- reactive oxygen species
- dna damage
- induced apoptosis
- dna methylation
- protein protein
- binding protein
- amino acid
- anti inflammatory
- cell death
- genome wide
- cell cycle arrest
- amyotrophic lateral sclerosis
- endoplasmic reticulum stress
- hydrogen peroxide
- copy number
- poor prognosis
- small molecule
- nitric oxide
- metabolic syndrome
- genome wide identification
- skeletal muscle
- dna repair
- diabetic rats
- atomic force microscopy
- high resolution
- heat stress
- heat shock protein