Loss of ERdj5 exacerbates oxidative stress in mice with alcoholic liver disease via suppressing Nrf2

Hong, Dong-Gyun; Song, Ga Yeon; Eom, Cheol Bin; Ahn, Jae-Hee; Kim, Sun Myoung; Shim, Aeri; Han, Yong-Hyun; Roh, Yoon-Seok; Han, Chang Yeob; Bae, Eun Ju; Ko, Hyun–Jeong; Yang, Yoon Mee

doi:10.1016/j.freeradbiomed.2022.03.027

Cited by 6 publications

(2 citation statements)

References 55 publications

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“…Excessive drinking can quickly induce body dysfunction, even premature death [ 3 ]. For example, alcoholic liver disease is the main cause of chronic liver disease [ 4 , 5 ]. Fatty liver is the early stage of alcoholic liver disease [ 6 ], mainly manifested in the liver’s excessive deposition of triglycerides, phospholipids and cholesterol esters [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Insight into Lotusine and Puerarin in Repairing Alcohol-Induced Metabolic Disorder Based on UPLC-MS/MS

Zhang

Yan

et al. 2022

IJMS

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Alcohol is an essential element in human culture. However, alcoholism has contributed to numerous health issues, including alcoholic fatty liver and sudden death. We found that the alkaloid lotusine possessed hepato- and neuroprotection against alcohol injuries. Lotusine showed comparable protective effects to puerarin, a widely recognized antagonist against alcohol damage. To better understand the metabolic response to alcohol injury and antagonist molecules, we applied sensitive zebrafish and LC-ESI-MS to collect metabolites related to alcohol, puerarin and lotusine exposure. LC-MS identified 119 metabolites with important physiological roles. Differential metabolomic analysis showed that alcohol caused abnormal expression of 82 metabolites (60 up-regulated and 22 down-regulated). These differential metabolites involved 18 metabolic pathways and modules, including apoptosis, necroptosis, nucleotide and fatty acid metabolism. Puerarin reversed seven metabolite variations induced by alcohol, which were related to necroptosis and sphingolipid metabolism. Lotusine was found to repair five metabolites disorders invoked by alcohol, mainly through nucleotide metabolism and glutathione metabolism. In phenotypic bioassay, lotusine showed similar activities to puerarin in alleviating behavioral abnormalities, neuroapoptosis and hepatic lipid accumulation induced by alcohol exposure. Our findings provided a new antagonist, lotusine, for alcohol-induced damage and explored the roles in repairing abnormal metabolism.

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Section: Introductionmentioning

confidence: 99%

Insight into Lotusine and Puerarin in Repairing Alcohol-Induced Metabolic Disorder Based on UPLC-MS/MS

Zhang

Yan

et al. 2022

IJMS

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“…Loss of Dnajc10 in mice results in increased reactive oxygen (ROS) production in mouse hepatocytes. 4 Given the critical need of ROS mitigation in maintenance of AML LSC, the impact of DNAJC10 silencing on AML LSC could be linked to impaired ROS mitigation. Irrespective of the underlying mechanism, Li et al 1 have clearly identified a promising target for eliminating AML LSC.…”

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confidence: 99%

Stressing the stem cell in acute myeloid leukemia

Borthakur

2023

haematol

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An antireductant approach ameliorates misfolded proinsulin-induced hyperglycemia and glucose intolerance in male Akita mice

Mattocks,

Ommi,

Malloy

et al. 2024

GeroScience

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Protein folding in the endoplasmic reticulum (ER) requires a high ratio of oxidized to reduced glutathione (GSSG/rGSH). Since the GSSG/rGSH depends on total glutathione (tGSH = GSSG + rGSH) levels, we hypothesized that limiting GSH biosynthesis will ameliorate protein misfolding by enhancing the ER oxidative milieu. As a proof-of-concept, we used DL-buthionine-(S,R)-sulfoximine (BSO) to inhibit GSH biosynthesis in Akita mice, which are prone to proinsulin misfolding. We conducted a 2-week intervention to investigate if BSO was safe and a 6-week intervention to find its effect on glucose intolerance. In both cohorts, male heterozygous Akita (AK) and wild-type (WT) mice were continuously administered 15 mM BSO. No adverse effects were observed on body weight, food intake, and water intake in either cohort. Unaltered levels of plasma aspartate and alanine aminotransferases, and cystatin-C, indicate that BSO was safe. BSO-induced decreases in tGSH were tissue-dependent with maximal effects in the kidneys, where it altered the expression of genes associated with GSH biosynthesis, redox status, and proteostasis. BSO treatment decreased random blood glucose levels to 80% and 67% of levels in untreated mice in short-term and long-term cohorts, respectively, and 6-h fasting blood glucose to 82% and 74% of levels in untreated mice, respectively. BSO also improved glucose tolerance by 37% in AK mice in the long-term cohort, without affecting insulin tolerance. Neither glucose tolerance nor insulin tolerance were affected in WT. Data indicate that BSO might treat misfolded proinsulin-induced glucose intolerance. Future studies should investigate the effect of BSO on proinsulin misfolding and if it improves glucose intolerance in individuals with Mutant Insulin Diabetes of Youth. Graphical abstract 1) Male heterozygous C57BL/6-Ins2Akita/J (AK) mice suffer from misfolded proinsulin-induced glucose intolerance. (a) Proinsulin misfolding occurs due to a genetic mutation in Ins2 gene that substitutes Cys with Tyr, (b) Due to heterozygosity, AK mice produce both wild-type and mutated proinsulin, (c) Mutated proinsulin forms aggregates with itself and with the bystander native proinsulin, (d) Proinsulin aggregation results in lower functional insulin, and (e) AK mice suffer from impaired glucose tolerance. 2) Treating mice with BSO improved glucose tolerance. (a) Mice were treated with continuous administration of 15 mM DL -buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione biosynthesis (b), BSO treatment increased the renal mRNA quantity of several genes involved in glutathione biosynthesis, glutathione redox status, and proteostasis, (c) we hypothesize that BSO-induced changes in cellular redox status and gene expression ameliorates proinsulin aggregation and increases the functional insulin levels in β-cells, and (d) BSO treatment significantly improved glucose intolerance in AK mice. Note: AUC - Area under the curve, GCL -γ-g-glutamylcysteine ligase, GS - Gluatthione synthetase.

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Loss of ERdj5 exacerbates oxidative stress in mice with alcoholic liver disease via suppressing Nrf2

Cited by 6 publications

References 55 publications

Insight into Lotusine and Puerarin in Repairing Alcohol-Induced Metabolic Disorder Based on UPLC-MS/MS

Insight into Lotusine and Puerarin in Repairing Alcohol-Induced Metabolic Disorder Based on UPLC-MS/MS

Stressing the stem cell in acute myeloid leukemia

An antireductant approach ameliorates misfolded proinsulin-induced hyperglycemia and glucose intolerance in male Akita mice

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