l‐Methionine activates Nrf2‐ARE pathway to induce endogenous antioxidant activity for depressing ROS‐derived oxidative stress in growing rats

Abstract

BACKGROUND Methionine is an essential sulfur‐containing amino acid. To elucidate the influence of l‐methionine on activation of the nuclear factor erythroid 2‐related factor 2–antioxidant responsive element (Nrf2‐ARE) antioxidant pathway to stimulate the endogenous antioxidant activity for depressing reactive oxygen species (ROS)‐derived oxidative stress, male Wistar rats were orally administered l‐methionine daily for 14 days. RESULTS With the intake of l‐methionine, Nrf2 was activated by l‐methionine through depressing Keap1 and Cul3, resulting in upregulation of ARE‐driven antioxidant expression (glutamate cysteine ligase catalytic subunit, glutamate cysteine ligase modulatory subunit, glutathione synthase (GS), catalase (CAT), superoxide dismutase (SOD), heme oxygenase 1, NAD(P)H:quinone oxidoreductase 1, glutathione reductase (GR), glutathione S‐transferase (GST), glutathione peroxidase (GPx)) with increasing l‐methionine availability. Upon activation of Nrf2, glutathione synthesis was increased through upregulated expression of methionine adenosyltransferase, S‐adenosylhomocysteine hydrolase, cystathionine β‐synthase, cystathionine γ‐lyse, glutamate cysteine ligase (GCL) and GS, while hepatic expressions of methionine sulfoxide reductases (MsrA, MsrB2, MsrB3) and hepatic enzyme activities (CAT, SOD, GCL, GR, GST, GPx) were uniformly stimulated with increasing consumption of l‐methionine. As a result, hepatic content of ROS and MDA were effectively reduced by l‐methionine intake. CONCLUSION The present study demonstrates that methionine availability plays a critical role in activation of the Nrf2‐ARE pathway to induce an endogenous antioxidant response for depressing ROS‐derived oxidative stress, which is primarily attributed to the stimulation of methionine sulfoxide reductase expression and glutathione synthesis. © 2019 Society of Chemical Industry

Rice Protein Exerts Anti-Inflammatory Effect in Growing and Adult Rats via Suppressing NF-κB Pathway

“…To explain this phenomenon, the view that the inflammation can be prevented by dietary antioxidants should be taken into account in this study [28]. It has been demonstrated that nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) can modulate the anti-inflammatory response through the inhibition of NF-κB and upregulate antioxidant responsive element (ARE)-dependent gene expressions, such as HO-1 [11,[29][30][31]. In light of this view, a satisfactory explanation could be drawn from our previous studies, in which rice protein could exert an antioxidant capacity via activation of Nrf2 and upregulation of HO-1 expression in adult rats [11].…”

“…According to our previous studies [6][7][8]11,24,29,30], animal studies (SCXK2012-0001, 8 February 2012) were approved and performed in conformity with the Guidelines of the Committee for the Experimental Animals of Harbin Institute of Technology (Harbin, China). Briefly, growing male Wistar rats (body weight 180-200 g) and adult male Wistar rats (body weight 390-410 g) were purchased from the Vital River Laboratories (Beijing Vital River Laboratory Animal Technology Co. Ltd., Beijing, China) and individually housed in metabolic cages in a room maintained at 22 ± 2 • C under a 12-h light-dark cycle (07:00-19:00 for light).…”

“…The analysis of ROS levels in the liver was according to our previous studies [11,24,29,30]. Briefly, ROS was determined by fluorescence of 2 , 7 -dichlorofluorescin diacetate (DCF-DA) as described by the manufacturer's protocol of the commercial kit (Nanjing Jiancheng Bioengineering Institute, Nanjing, China).…”

Rice protein reduces DNA damage by activating the p53 pathway and stimulating endogenous antioxidant response in growing and adult rats

“…As a sensor for oxidative stress, Nrf2 is tightly regulated by the Kelch‐like ECH‐associated protein 1 (Keap1) . Hence, the activation of Nrf2‐Keap1 pathway is regarded as playing a key role in inducing an antioxidant response to scavenge ROS . After 2 weeks' feeding, rice protein suppressed the expressions of Keap1 in protein and genes, leading to the activation of the Nrf2‐keap1 pathway in growing and adult rats fed with rice proteins.…”

“…45,46 Hence, the activation of Nrf2-Keap1 pathway is regarded as playing a key role in inducing an antioxidant response to scavenge ROS. 28,44,47 After 2 weeks' feeding, rice protein suppressed the expressions of Keap1 in protein and genes, leading to the activation of the Nrf2-keap1 pathway in growing and adult rats fed with rice proteins. Consequently, the ARE-driven antioxidant expression of CAT, SOD and GPx could be stimulated by rice protein feeding, showing a significantly positive correlation between nuclear contents of Nrf2 and the expressions of CAT (r = 0.8424, P < 0.05), of SOD (r = 0.8255, P < 0.05), and of GPx (r = 0.7991, P < 0.05), respectively.…”