MicroRNA-mediated regulation of glutathione and methionine metabolism and its relevance for liver disease

Lu, Shelly C.; Mato, José M.; Espinosa‐Díez, Cristina; Lamas, Santiago

doi:10.1016/j.freeradbiomed.2016.03.021

Cited by 33 publications

(15 citation statements)

References 71 publications

(89 reference statements)

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“…Furthermore, data on the upregulated expression of GCLC, GCLM and GS by Nrf2 activation have provided a mechanistic explanation for the critical role of Nrf2 in the induction of endogenous GSH synthesis. It is worth noting that Lu et al have also highlighted an important role of the transsulfuration pathway for GSH synthesis via the Nrf2 pathway through regulation of microRNA in methionine metabolism, further supporting our findings that l ‐methionine availability is a critical factor in the stimulation of GSH synthesis via activating Nrf2‐ARE pathway for depressing ROS‐derived oxidative stress.…”

Section: Discussionsupporting

confidence: 89%

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

Wang

Liang

et al. 2019

J Sci Food Agric

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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

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Section: Discussionsupporting

confidence: 89%

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

Wang

Liang

et al. 2019

J Sci Food Agric

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“…This is the rate-limiting step for threonine utilization by the liver ( 53 , 54 ). Methionine is a metabolite that is important for GSH synthesis in the liver ( 55 ). Oral administration of methionine at high doses was reported to markedly elevate the level of homocysteine in rat plasma, while long-term MT administration significantly reduced homocysteine levels ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of potential biomarkers in cholestasis and the therapeutic effect of melatonin by metabolomics, multivariate data and pathway analyses

et al. 2018

Int J Mol Med

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The present study investigated the anti-cholestatic effect of melatonin (MT) against α-naphthyl isothiocyanate (ANIT)-induced liver injury in rats and screened for potential biomarkers of cholestasis. Rats were administered ANIT by intraperitoneal injection and then sacrificed 36 h later. Serum biochemical parameters were measured and liver tissue samples were subjected to histological analysis. Active components in the serum were identified by gas chromatography-mass spectrometry, while biomarkers and biochemical pathways were identified by multivariate data analysis. The results revealed that the serum levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, direct bilirubin, γ-glutamyl transpeptidase, and alkaline phosphatase were reduced in rats with ANIT-induced cholestasis that were treated with MT. The histological observations indicated that MT had a protective effect against ANIT-induced hepatic tissue damage. Metabolomics analysis revealed that this effect was likely to be associated with the regulation of compounds related to MT synthesis and catabolism, and amino acid metabolism, including 5-aminopentanoate, 5-methoxytryptamine, L-tryptophan, threonine, glutathione, L-methionine, and indolelactate. In addition, principal component analysis demonstrated that the levels of these metabolites differed significantly between the MT and control groups, providing further evidence that they may be responsible for the effects induced by MT. These results provide an insight into the mechanisms underlying cholestasis development and highlight potential biomarkers for disease diagnosis.

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“…Homeostasis of intracellular glutathione is not solely regulated by de novo synthesis, but it also by several factors including cellular export, utilization, and recycling (Lu S. C. et al, 2016 ). This redox cycle is recognized as the glutathione cycle which comprises of glutathione, together with other redox-related enzymes acts as the first defense against overproduction of harmful ROS in addition to repairing ROS-induced damage (Schieber and Chandel, 2014 ).…”

Section: Role Of Antioxidants In the Prevention Of Age-related Diseasmentioning

confidence: 99%

Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

et al. 2018

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Aging is the progressive loss of organ and tissue function over time. Growing older is positively linked to cognitive and biological degeneration such as physical frailty, psychological impairment, and cognitive decline. Oxidative stress is considered as an imbalance between pro- and antioxidant species, which results in molecular and cellular damage. Oxidative stress plays a crucial role in the development of age-related diseases. Emerging research evidence has suggested that antioxidant can control the autoxidation by interrupting the propagation of free radicals or by inhibiting the formation of free radicals and subsequently reduce oxidative stress, improve immune function, and increase healthy longevity. Indeed, oxidation damage is highly dependent on the inherited or acquired defects in enzymes involved in the redox-mediated signaling pathways. Therefore, the role of molecules with antioxidant activity that promote healthy aging and counteract oxidative stress is worth to discuss further. Of particular interest in this article, we highlighted the molecular mechanisms of antioxidants involved in the prevention of age-related diseases. Taken together, a better understanding of the role of antioxidants involved in redox modulation of inflammation would provide a useful approach for potential interventions, and subsequently promoting healthy longevity.

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MicroRNA-mediated regulation of glutathione and methionine metabolism and its relevance for liver disease

Cited by 33 publications

References 71 publications

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

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

Identification of potential biomarkers in cholestasis and the therapeutic effect of melatonin by metabolomics, multivariate data and pathway analyses

Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

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