Isocitrate dehydrogenase 2 deficiency aggravates prolonged high-fat diet intake-induced hypertension

Noh, Mi Ra; Kong, Min Jung; Han, Sang Jun; Kim, Jee In; Park, Kwon Moo

doi:10.1016/j.redox.2020.101548

Cited by 29 publications

(21 citation statements)

References 57 publications

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“…Catalase exists in the cytoplasm and can reduce fat accumulation without oxidative damage and control the peroxisomal H 2 O 2 that degrades hepatic fatty acids, thus maintaining the optimal metabolic balance ( 43 ). Nicotinamide adenine dinucleotide phosphate acts as a hydrogen transmitter in many chemical reactions (e.g., electron transport chain) and is an essential cofactor in the reduction of GSH to its reduced form ( 44 ). The level of reduced GSH fluctuates with the content of NADPH, and the decreased NADPH leads to increased ROS and results in oxidative damage to tissues.…”

Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effect of Lactobacillus plantarum HFY09 on Ethanol-Induced Liver Injury in Mice

et al. 2021

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Lactobacillus plantarum is a bacterial strain that is used as a probiotic with health-promoting effects. Our study investigated the hepatoprotective effect of Lactobacillus plantarum HFY09 (LP-HFY09) in mice with ethanol-induced liver injury. The protection afforded by LP-HFY09 was evaluated by observing the morphology of hepatic tissue and measuring liver lipid indexes and function indexes, levels of anti-oxidative enzymes, and anti-inebriation enzymes, as well as oxidative metabolism-related gene expression. Gavage administration of LP-HFY09 [1 × 109 CFU/kg body weight (bw)] limited the loss of bw, alcohol damage to the liver, and maintained the normal hepatic tissue morphology. Lactobacillus plantarum HFY09 intervention in ethanol-induced mice led to decreases in serum triglyceride (TG), total cholesterol (TC), aspartic transaminase, alanine transaminase, hyaluronidase (HAase), and precollagen III (PC III), and increases in liver alcohol dehydrogenase (ADH), and acetaldehyde dehydrogenase (ALDH). Lactobacillus plantarum HFY09 assisted with alleviating inflammation by elevating the level of interleukin 10 (IL-10) and decreasing the levels of pro-inflammatory factors [IL-6, IL-1β, and tumor necrosis factor-α (TNF)-α]. Lactobacillus plantarum HFY09 significantly elevated hepatic levels of superoxide dismutase (SOD) and glutathione (GSH), and decreased liver malondialdehyde (MDA) from 3.45 to 1.64 nmol/mg protein. Lactobacillus plantarum HFY09 exhibited an overall strong regulatory effect on liver protection when compared to that of commercial Lactobacillus delbrueckii subsp. bulgaricus. The hepatoprotective effect of LP-HFY09 was reflected by the upregulated expression of peroxisome proliferator activated-receptors α, SOD1, SOD2, glutathione peroxidase (GSH-Px), nicotinamide adenine dinucleotide phosphate (NADPH), and catalase (CAT), and the downregulated expression of cyclooxygenase-1 (COX1), c-Jun N-terminal kinase (JNK), and extracellular regulated protein kinases (ERK). Administration of LP-HFY09 at a concentration of 1.0 × 109 CFU/kg bw could be a potential intervention, for people who frequently consume alcohol.

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Section: Discussionmentioning

confidence: 99%

Hepatoprotective Effect of Lactobacillus plantarum HFY09 on Ethanol-Induced Liver Injury in Mice

et al. 2021

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“…In acute kidney injury by cisplatin, IDH2 levels are decreased; moreover, IDH1/2 activities are reduced, but with no IDH3 [ 89 ]; in a similar way, in I/R-induced AKI it has been reported that IDH1/2 are reduced, as well their function [ 83 , 90 ]; on the other hand in UUO-induced CKD, IDH2 levels also are reduced, and in diabetic nephropathy, also IDH2 activity is diminished [ 91 ]. Thus, demonstrating that IDH2 activity reduction is a common characteristic in all of these pathologies.…”

Section: Alpha-ketoglutaratementioning

confidence: 99%

“…Besides, genetic deletion of IDH2 exacerbates renal damage by increasing oxidative stress and leukocyte infiltration in I/R and cisplatin-induced AKI and UUO-induced CKD models [ 83 , 89 , 92 ], reflecting an antioxidant protective effect of this enzyme additional to its function of AKG synthesis. Additionally, an interesting finding is that in diabetic nephropathy, IDH2 deficiency also increases the expression of renin, angiotensin II type 1 receptor, angiotensinogen, and angiotensin-converting enzyme in renal tissue, as well renin and angiotensin II levels in plasma, promoting hypertension derived from oxidative stress [ 91 ].…”

Section: Alpha-ketoglutaratementioning

confidence: 99%

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

et al. 2021

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Mitochondria are complex organelles that orchestrate several functions in the cell. The primary function recognized is energy production; however, other functions involve the communication with the rest of the cell through reactive oxygen species (ROS), calcium influx, mitochondrial DNA (mtDNA), adenosine triphosphate (ATP) levels, cytochrome c release, and also through tricarboxylic acid (TCA) metabolites. Kidney function highly depends on mitochondria; hence mitochondrial dysfunction is associated with kidney diseases. In addition to oxidative phosphorylation impairment, other mitochondrial abnormalities have been described in kidney diseases, such as induction of mitophagy, intrinsic pathway of apoptosis, and releasing molecules to communicate to the rest of the cell. The TCA cycle is a metabolic pathway whose primary function is to generate electrons to feed the electron transport system (ETS) to drives energy production. However, TCA cycle metabolites can also release from mitochondria or produced in the cytosol to exert different functions and modify cell behavior. Here we review the involvement of some of the functions of TCA metabolites in kidney diseases.

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“…Mice lacking IDH2 deletion are viable and healthy but are sensitized to mitochondrial oxidative damage in the hepatocytes resulting from ischemia-reperfusion injury or high fat diet. [40,41]…”

Section: Normal Functions Of the Idh Enzymesmentioning

confidence: 99%

Biology of IDH mutant cholangiocarcinoma

Shi

Merritt

et al. 2022

Hepatology

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Isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) are the most frequently mutated metabolic genes across human cancers. These hotspot gainof-function mutations cause the IDH enzyme to aberrantly generate high levels of the oncometabolite, R-2-hydroxyglutarate, which competitively inhibits enzymes that regulate epigenetics, DNA repair, metabolism, and other processes. Among epithelial malignancies, IDH mutations are particularly common in intrahepatic cholangiocarcinoma (iCCA). Importantly, pharmacological inhibition of mutant IDH (mIDH) 1 delays progression of mIDH1 iCCA, indicating a role for this oncogene in tumor maintenance. However, not all patients receive clinical benefit, and those who do typically show stable disease rather than significant tumor regressions. The elucidation of the oncogenic functions of mIDH is needed to inform strategies that can more effectively harness mIDH as a therapeutic target. This review will discuss the biology of mIDH iCCA, including roles of mIDH in blocking cell differentiation programs and suppressing antitumor immunity, and the potential relevance of these effects to mIDH1-targeted therapy. We also cover opportunities for synthetic lethal therapeutic interactions that harness the altered cell state provoked by mIDH1 rather than inhibiting the mutant enzyme. Finally, we highlight key outstanding questions in the biology of this fascinating and incompletely understood oncogene.

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Isocitrate dehydrogenase 2 deficiency aggravates prolonged high-fat diet intake-induced hypertension

Cited by 29 publications

References 57 publications

Hepatoprotective Effect of Lactobacillus plantarum HFY09 on Ethanol-Induced Liver Injury in Mice

Hepatoprotective Effect of Lactobacillus plantarum HFY09 on Ethanol-Induced Liver Injury in Mice

Involvement of Tricarboxylic Acid Cycle Metabolites in Kidney Diseases

Biology of IDH mutant cholangiocarcinoma

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