Upregulation and stabilization of senescence marker protein-30 by epigallocatechin gallate against <i>tert</i>-butyl hydroperoxide-induced liver injury <i>in vitro</i> and <i>in vivo</i>

Abstract

Senescence marker protein-30 (SMP30), a novel ageing marker, suppresses oxidative stress in the liver. However, studies on phytochemical-mediated regulation of SMP30 expression are lacking. Here, we showed that epigallocatechin gallate (EGCg), a polyphenol abundant in green tea, positively regulates SMP30 expression in the rat hepatoma-derived Fao cells. EGCg maintained SMP30 expression even in the presence of cycloheximide, a protein synthesis inhibitor. Furthermore, treatment of cells with tert -butyl hydroperoxide ( tert -BHP), an oxidative promoter, decreased SMP30 expression and ERK1/2 phosphorylation, while EGCg treatment inhibited these effects. Male mice (7-week-old) were divided into 4 groups—Control (saline), tert -BHP (1.5 mmol/kg tert -BHP), EGCg + tert -BHP (30 mg/kg/day of EGCg and 1.5 mmol/kg tert -BHP), and EGCg (30 mg/kg/day). After oral EGCg administration for 6 consecutive days, EGCg + tert -BHP group mice were administered tert -BHP. The tert -BHP-administered mice showed decreased SMP30 expression in the liver and increased aspartate aminotransferase and alanine transaminase (hepatic injury marker enzymes) activities; however, EGCg treatment attenuated these changes. Thus, EGCg-induced SMP30 upregulation may alleviate tert -BHP-induced liver injury. The findings of this study offer new perspectives of the anti-ageing properties of EGCg.

Resveratrol Upregulates Senescence Marker Protein 30 by Activating AMPK/Sirt1-Foxo1 Signals and Attenuating H₂O₂-Induced Damage in FAO Rat Liver Cells

“…3D). Our results are in line with previous findings of SMP30 downregulation caused by oxidative stress (8,24,25). Antioxidant procyanidins also protect FAO cells against damage caused by H2O2-induced oxidative stress (26,27).…”

“…1B). Inoue et al reported that the antioxidant epigallocatechin gallate (EGCG) upregulated SMP30 expression (8). However, the ability of other factors in food to positively regulate SMP30 expression has remained unknown.…”

“…Therefore, decreasing of SMP30 expression results in the accumulation of reactive oxidative species (ROS) reactant substance. In fact, we recently reported that the antioxidant epigallocatechin gallate (EGCG) upregulates SMP30 expression and attenuating of t-BHP-induced oxidative stress (8). Thus, upregulation of SMP30 by food factor may be possible to protect against oxidative stress.…”

Release of SMP30 in Extracellular Vesicles under Conditions of Ascorbic Acid Deficiency Is Involved with Acute Phase Response in ODS Rat

“…Specifically, the liver in SMP30 knockout mice is highly susceptible to inflammatory molecules such as tumor necrosis factor-a (TNF-a)-and Fas-induced apoptosis (5). We previously reported that SMP30 expression was downregulated in the livers of tert-BHP-administered mice, resulting in the promotion of liver injury (6). Other researchers have reported that acute oxidative stress, such as carbon tetrachloride, suppresses SMP30 expression in the liver (7).…”