Depletion of Tip60/Kat5 affects the hepatic antioxidant system in mice

Abstract

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.

The Hepatic Antioxidant System Damage Induced with the Cafeteria (CAF) Diet Is Largely Counteracted Using SCD Probiotics during Development of Male Wistar Rats

“…The CAF diet led to statistically significant increases in various metabolite levels (MDA, GSH, and GSSG), and SCD Probiotics effectively reversed this effect. Unusual changes in MDA and GSH levels are crucial indicators of lipid peroxidation and concretization [16,29]. While it mostly had no significant effect when administered alone, SCD Probiotics notably reversed the impact of the CAF diet.…”

“…The primary choice of a healthy cell to maintain redox balance by maintaining a reduced environment is to support the GSH pool [30,31]. Changes in cellular GSH and the GSH/GSSG ratio are associated with oxidative stress and cancer development [16].…”

“…To ensure homogeneity, each tissue was completely chopped into tiny pieces by mincing with a sterile scalpel. The samples were prepared using the required amounts of these homogenous solid tissues [15,16]. SCD Probiotics are a product of a food manufacturing company and are used as a food supplement (Essential Probiotics XI-500 mL H.S.…”

“…The measurement of MDA serves as a critical marker showing the extent of lipid peroxidation in a cell. Consequently, the determination of MDA holds significance in the acquisition of data pertaining to a series of issues, including oxidative stress, toxicity, and cancerization [16]. Various dietary regimens were administered to male Wistar rats during their development period for 5 weeks by focusing on assessing their primary impact on the hepatic antioxidant system prior to the onset of obesity.…”

“…Based on the importance of the reduced environment, GSH generation is the cell's primary choice to maintain the cellular glutathione pool. Hence, the cellular glutathione system plays a pivotal role in controlling the levels of both reduced glutathione (GSH) and oxidized glutathione (GSSG) and due to the link of the deviations in the GSH concentration and GSH/GSSG ratio with oxidative stress and cancer, firm regulation of the GSH/GSSG ratio is essential for maintaining the balance within the antioxidant system [16]. For this reason, the effects of various diet combinations on the concentration of GSH and GSSG were investigated.…”