Regulation of G6PD acetylation by KAT9/SIRT2 modulates NADPH homeostasis and cell survival during oxidative stress

Wang, Yi Ping; Zhou, Li; Zhao, Yuzheng; Wang, Shi Wen; Chen, Lei Lei; Liu, Li Xia; Ling, Zhi Qiang; Hu, Fu Jun; Sun, Yi; Zhang, Jing Ye; Yang, Chen; Yang, Yi; Xiong, Yue; Guan, Kun Liang; Ye, Dan

doi:10.1002/embj.201387224

Cited by 201 publications

(267 citation statements)

References 86 publications

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“…This cell line has a glucose 6-phosphate dehydrogenase (G6PD) A phenotype, meaning it lacks the proper functioning of this enzyme in the pentose phosphate pathway. 13 G6PD is the rate-limiting enzyme in this pathway; its deficiency blocks the conversion of glucose-6-phosphate to 6-phosphoglucono-D-lactone and in the process prevents the conversion of NADPH to NADP + , a required step in GSH synthesis. 14 This suggests that a GSH deficiency may play an important role in potentiating the activity, something previously demonstrated when A2780 cells were co-incubated with low levels of the GSH inhibitor, L-buthionine sulfoximine.…”

Section: Antiproliferative Activitymentioning

confidence: 99%

Pharmaco-genomic investigations of organo-iridium anticancer complexes reveal novel mechanism of action

et al. 2018

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Section: Antiproliferative Activitymentioning

confidence: 99%

Pharmaco-genomic investigations of organo-iridium anticancer complexes reveal novel mechanism of action

et al. 2018

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“…Abnormalities in its levels may have pathological implications. It also plays vital roles in managing oxidative stress within cells [38] . This suggests that caffeine mechanism might stimulate basal glucose metabolism more, and this is logical as it is widely acclaimed to enhance performance especially at moderate doses.…”

Section: Effects Of Caffeine and Cannabis On Enzymesmentioning

confidence: 99%

Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats

Owolabi

Olatunji

Olanrewaju³

2017

Ann Neurosci

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Background: Caffeine and cannabis are globally consumed and abused psychoactive substances. While caffeine is legally used in various forms, including in tea and coffee as beverages, it is also consumed in soda and energy drinks as additives. Cannabis, on the other hand, is considered illegal in most countries; albeit, it is being consumed globally particularly by adolescents. Purpose: The adolescent stage marks a critical stage of brain development and maturation. Influences of agents on the brain at this stage may affect neuronal structural and functional attributes. To this end, the current experiment considered the effects of cannabis and caffeine on selected key neurotransmitters and enzymes in the brain tissues after regimented caffeine and cannabis treatment for 21 days. Methods: A total of 72 juvenile Wistar rats that were approximately 40 days old were divided into 6 groups A-F. The group A served as the control. Other groups were administered various dosages of caffeine or cannabis in distilled water, using oral gavages as follows: group B animals received 100 mg/kg body weight of caffeine, group C animals received 50 mg/kg body weight of caffeine, group D animals received 500 mg/kg body weight of cannabis, group E animals received 200 mg/kg body weight of cannabis, and group F received a low dose of cannabis (200 mg/kg body weight) plus a low dose of caffeine (50 mg/kg body weight). The animals were killed by cervical dislocation 24 h after the last administration. The brain tissues were excised and homogenized. The enzymes cytochrome C oxidase and glucose-6-phosphate dehydrogenase were assayed to observe tissue energy metabolism while the neurotransmitters gamma-amino butyric acid (GABA), glutamate, and dopamine were assayed to observe the effects of the psychoactive substances on their activities relative to mental activities. Results: GABA, glutamate, and dopamine were generally higher in the treated groups of animals. The levels of G-6-PDH were higher in all treated animals' brains. Caffeine produced quite more significant effects relative to cannabis and the combination of both increased the level of G-6-PDH significantly. Conclusion: Results showed that caffeine and cannabis influenced the activities of the enzymes and neurotransmitters in the brain. Both stimulants altered brain chemistry relative to the tested enzymes and neurotransmitters.

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“…G6PD is the first enzyme of the PPP and it catalyzes the oxidation of glucose-6-phosphate to 6-phosphogluconolactone [Zhao et al, 2014]. This enzyme is a key modulator of the metabolic rate in the PPP, a route that provides the organism with NADPH, which is involved in several biological processes, but mainly as a reducing equivalent donor for fatty acid synthesis and ri-bose-5-phosphate for nucleotide synthesis [Wang et al, 2014b]. G6PD activity has a fundamental role in counteracting oxidative stress by maintaining a reduced environment for the proper functioning of the cell.…”

Section: Discussionmentioning

confidence: 99%

PPAR Agonists Promote the Differentiation of Porcine Bone Marrow Mesenchymal Stem Cells into the Adipogenic and Myogenic Lineages

Pérez-Serrano

González-Dávalos²,

Lozano-Flores³

et al. 2016

Cells Tissues Organs

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Purpose: The aim of this work was to evaluate the effect of PPAR agonists on the differentiation and metabolic features of porcine mesenchymal stem cells induced to the adipogenic or myogenic lineages. Methods: Bone marrow MSCs from neonate pigs were isolated and identified by cell proliferation, cell surface markers or the gene expression of stem cells (CD44, CD90, CD105 or Oct4 and Nanog, respectively). Cells were differentiated into adipose or muscle cells and treated with the PPAR agonists; adipogenic and myogenic differentiation was promoted by adding these compounds. The expression of PPARγ (an adipose marker) and MyoD1 and MyHC (muscle markers), metabolic changes and expression levels of metabolic enzymes involved in glycolysis, lipogenesis, lipolysis and the pentose phosphate pathway were tested by qPCR. Results: MSCs from neonate pigs exhibited high proliferation and were positive for CD44, CD90 and CD105 markers and Oct4 and Nanog expression. The treatment that promoted the highest expression of PPARγ was 50 µM of conjugated linoleic acid (CLA) c9 t11 (6.44 ± 0.69-fold, p ≤ 0.0001) in the adipose differentiation, and upregulation of HX2, ACCAα, ATGL, LPL and G6DP (p ≤ 0.0001) and downregulation of PFK and ACCAβ (p ≤ 0.0001) were found. For muscle differentiation, the best treatment was 50 µM of CLA c10 t12 (59.72 ± 4.72-fold, p ≤ 0.0001), and metabolic changes were upregulation of PFK, ACCAβ, G6DP, CPT1 and PPARβ/δ (p ≤ 0.0001), but no effect was observed with HX2 and ACCAα (p ≥ 0.05). Conclusions: Our results suggest that differentiated cells exhibit a typical cell lineage metabolism and higher efficiencies both in anabolism and catabolism.

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Regulation of G6PD acetylation by KAT9/SIRT2 modulates NADPH homeostasis and cell survival during oxidative stress

Cited by 201 publications

References 86 publications

Pharmaco-genomic investigations of organo-iridium anticancer complexes reveal novel mechanism of action

Pharmaco-genomic investigations of organo-iridium anticancer complexes reveal novel mechanism of action

Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats

PPAR Agonists Promote the Differentiation of Porcine Bone Marrow Mesenchymal Stem Cells into the Adipogenic and Myogenic Lineages

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