scholarly journals Mitochondrial dysfunction, AMPK activation and peroxisomal metabolism: A coherent scenario for non-canonical 3-methylglutaconic acidurias

Biochimie ◽  
2020 ◽  
Vol 168 ◽  
pp. 53-82 ◽  
Author(s):  
Joseph Vamecq ◽  
Bérengère Papegay ◽  
Vincent Nuyens ◽  
Jean Boogaerts ◽  
Oberdan Leo ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Ampk Activation

scholarly journals Different Effects of Metformin and A769662 on Sodium Iodate-Induced Cytotoxicity in Retinal Pigment Epithelial Cells: Distinct Actions on Mitochondrial Fission and Respiration

Antioxidants ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 1057
Author(s):  
Chi-Ming Chan ◽  
Ponarulselvam Sekar ◽  
Duen-Yi Huang ◽  
Shu-Hao Hsu ◽  
Wan-Wan Lin
Keyword(s):  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Respiration ◽  
Retinal Pigment ◽  
Mitochondrial Fission ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Mitochondrial Morphology ◽  
Ros Production ◽  
Ampk Activation ◽  
Sodium Iodate

Oxidative stress-associated retinal pigment epithelium (RPE) cell death is critically implicated in the pathogenesis of visual dysfunction and blindness of retinal degenerative diseases. Sodium iodate (NaIO3) is an oxidative retinotoxin and causes RPE damage. Previously, we found that NaIO3 can induce human ARPE-19 cell death via inducing mitochondrial fission and mitochondrial dysfunction. Although metformin has been demonstrated to benefit several diseases possibly via AMP-activated protein kinase (AMPK) activation, it remains unknown how AMPK affects retinopathy in NaIO3 model. Therefore, in this study, we compared the effects of metformin and AMPK activator A769662 on NaIO3-induced cellular stress and toxicity. We found that A769662 can protect cells against NaIO3-induced cytotoxicity, while metformin exerts an enhancement in cell death. The mitochondrial reactive oxygen species (ROS) production as well as mitochondrial membrane potential loss induced by NaIO3 were not altered by both agents. In addition, NaIO3-induced cytosolic ROS production, possibly from nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation and counteracting cell death, was not altered by A769662 and metformin. Notably, NaIO3-induced mitochondrial fission and inhibition of mitochondrial respiration for ATP turnover were reversed by A769662 but not by metformin. In agreement with the changes on mitochondrial morphology, the ERK-Akt signal axis dependent Drp-1 phosphorylation at S616 (an index of mitochondrial fission) under NaIO3 treatment was blocked by A769662, but not by metformin. In summary, NaIO3-induced cell death in ARPE cells primarily comes from mitochondrial dysfunction due to dramatic fission and inhibition of mitochondrial respiration. AMPK activation can exert a protection by restoring mitochondrial respiration and inhibition of ERK/Akt/Drp-1 phosphorylation, leading to a reduction in mitochondrial fission. However, inhibition of respiratory complex I by metformin might deteriorate mitochondrial dysfunction and cell death under NaIO3 stress.

AMPK activation by isorhamnetin protects hepatocytes against oxidative stress and mitochondrial dysfunction

2014 ◽  
Vol 740 ◽  
pp. 634-640 ◽  
Author(s):  
Guang-Zhi Dong ◽  
Ju-Hee Lee ◽  
Sung Hwan Ki ◽  
Ji Hye Yang ◽  
Il Je Cho ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Ampk Activation

scholarly journals Sirt6 Suppresses High Glucose-Induced Mitochondrial Dysfunction and Apoptosis in Podocytes through AMPK Activation

2019 ◽  
Vol 15 (3) ◽  
pp. 701-713 ◽  
Author(s):  
Yanqin Fan ◽  
Qian Yang ◽  
Yingjie Yang ◽  
Zhao Gao ◽  
Yiqiong Ma ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
High Glucose ◽  
Ampk Activation

scholarly journals Exercise Preconditioning Blunts Early Atrogenes Expression and Atrophy in Gastrocnemius Muscle of Hindlimb Unloaded Mice

2021 ◽  
Vol 23 (1) ◽  
pp. 148
Author(s):  
Lorenza Brocca ◽  
Maira Rossi ◽  
Monica Canepari ◽  
Roberto Bottinelli ◽  
Maria Antonietta Pellegrino
Keyword(s):  
Mitochondrial Dysfunction ◽  
Endurance Exercise ◽  
Time Course ◽  
Gastrocnemius Muscle ◽  
Mitochondrial Dynamics ◽  
Hindlimb Unloading ◽  
Primary Role ◽  
Ampk Activation ◽  
Exercise Preconditioning ◽  
Muscle Protection

A large set of FoxOs-dependent genes play a primary role in controlling muscle mass during hindlimb unloading. Mitochondrial dysfunction can modulate such a process. We hypothesized that endurance exercise before disuse can protect against disuse-induced muscle atrophy by enhancing peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) expression and preventing mitochondrial dysfunction and energy-sensing AMP-activated protein kinase (AMPK) activation. We studied cross sectional area (CSA) of muscle fibers of gastrocnemius muscle by histochemistry following 1, 3, 7, and 14 days of hindlimb unloading (HU). We used Western blotting and qRT-PCR to study mitochondrial dynamics and FoxOs-dependent atrogenes’ expression at 1 and 3 days after HU. Preconditioned animals were submitted to moderate treadmill exercise for 7 days before disuse. Exercise preconditioning protected the gastrocnemius from disuse atrophy until 7 days of HU. It blunted alterations in mitochondrial dynamics up to 3 days after HU and the expression of most atrogenes at 1 day after disuse. In preconditioned mice, the activation of atrogenes resumed 3 days after HU when mitochondrial dynamics, assessed by profusion and pro-fission markers (mitofusin 1, MFN1, mitofusin 2, MFN2, optic atrophy 1, OPA1, dynamin related protein 1, DRP1 and fission 1, FIS1), PGC1α levels, and AMPK activation were at a basal level. Therefore, the normalization of mitochondrial dynamics and function was not sufficient to prevent atrogenes activation just a few days after HU. The time course of sirtuin 1 (SIRT1) expression and content paralleled the time course of atrogenes’ expression. In conclusion, seven days of endurance exercise counteracted alterations of mitochondrial dynamics and the activation of atrogenes early into disuse. Despite the normalization of mitochondrial dynamics, the effect on atrogenes’ suppression died away within 3 days of HU. Interestingly, muscle protection lasted until 7 days of HU. A longer or more intense exercise preconditioning may prolong atrogenes suppression and muscle protection.

Two isoprenylated flavonoids from Dorstenia psilurus activate AMPK, stimulate glucose uptake, inhibit glucose production and lower glycemia

2019 ◽  
Vol 476 (24) ◽  
pp. 3687-3704 ◽  
Author(s):  
Aphrodite T. Choumessi ◽  
Manuel Johanns ◽  
Claire Beaufay ◽  
Marie-France Herent ◽  
Vincent Stroobant ◽  
...  
Keyword(s):  
Glucose Uptake ◽  
Human Cancer ◽  
Glucose Production ◽  
Liver Mitochondria ◽  
New Drugs ◽  
Structural Isomer ◽  
Rat Liver Mitochondria ◽  
Ionization Mass ◽  
Ampk Activation ◽  
Starting Point

Root extracts of a Cameroon medicinal plant, Dorstenia psilurus, were purified by screening for AMP-activated protein kinase (AMPK) activation in incubated mouse embryo fibroblasts (MEFs). Two isoprenylated flavones that activated AMPK were isolated. Compound 1 was identified as artelasticin by high-resolution electrospray ionization mass spectrometry and 2D-NMR while its structural isomer, compound 2, was isolated for the first time and differed only by the position of one double bond on one isoprenyl substituent. Treatment of MEFs with purified compound 1 or compound 2 led to rapid and robust AMPK activation at low micromolar concentrations and increased the intracellular AMP:ATP ratio. In oxygen consumption experiments on isolated rat liver mitochondria, compound 1 and compound 2 inhibited complex II of the electron transport chain and in freeze–thawed mitochondria succinate dehydrogenase was inhibited. In incubated rat skeletal muscles, both compounds activated AMPK and stimulated glucose uptake. Moreover, these effects were lost in muscles pre-incubated with AMPK inhibitor SBI-0206965, suggesting AMPK dependency. Incubation of mouse hepatocytes with compound 1 or compound 2 led to AMPK activation, but glucose production was decreased in hepatocytes from both wild-type and AMPKβ1−/− mice, suggesting that this effect was not AMPK-dependent. However, when administered intraperitoneally to high-fat diet-induced insulin-resistant mice, compound 1 and compound 2 had blood glucose-lowering effects. In addition, compound 1 and compound 2 reduced the viability of several human cancer cells in culture. The flavonoids we have identified could be a starting point for the development of new drugs to treat type 2 diabetes.

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