Ischemia/reperfusion-induced upregulation of TIGAR in brain is mediated by SP1 and modulated by ROS and hormones involved in glucose metabolism

Sun, Meiling; Li, Mei; Huang, Qiao; Han, Feng; Gu, Jin-Hua; Xie, Jiaming; Han, Rong; Qin, Zheng‐Hong; Zhou, Zhipeng

doi:10.1016/j.neuint.2014.09.006

Cited by 34 publications

(21 citation statements)

References 39 publications

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“…These could be caused by different detection methods. In our previous study, we reported that NADPH reduced H 2 O 2 toxicity in cultured primary neurons through reducing ROS [32]. In this study, we also observed potent neuroprotective effects of NADPH in cultured dopaminergic MES23.5 cells and SH-SY5Y cells.…”

Section: Discussionsupporting

confidence: 74%

NADPH ameliorates MPTP-induced dopaminergic neurodegeneration through inhibiting p38MAPK activation

Zhou

Zhu

et al. 2018

Acta Pharmacol Sin

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Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Although the pathogenic mechanism underlying PD remains largely unknown, decreased nigral glutathione (GSH) in postmortem brains of PD patients supports the presence of oxidative stress in PD. We found that Nicotinamide adenine dinucleotide phosphate (NADPH), which is important for maintaining the level of GSH, protected dopaminergic (DA) neurons from neurotoxicity of MPTP/MPP. In the present study, NADPH prevented DA neurons from MPTP toxicity with increased GSH and decreased reactive oxygen species (ROS) levels in the ventral midbrain of mice, and improved motor activity. Our present results demonstrated that NADPH inhibited the phosphorylation of p38MAPK, decreased the level of TP53 protein, and inhibited TP53 nuclear translocation in DA neurons of SNpc and in MES23.5 cells. Furthermore, NADPH decreased the protein level of TP53 target gene, Bax, cleavage of PARP, and nuclei condensation. Taken together, NADPH abrogated MPTP-induced p38MAPK phosphorylation, TP53 nuclear translocation, and Bax induction, and finally, MPTP/MPP-induced apoptosis of DA neurons. This study suggests that NADPH may be a novel therapeutic candidate for PD.

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Section: Discussionsupporting

confidence: 74%

NADPH ameliorates MPTP-induced dopaminergic neurodegeneration through inhibiting p38MAPK activation

Zhou

Zhu

et al. 2018

Acta Pharmacol Sin

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“…TIGAR expression is also regulated by the transcription factors MYC and SP1 (31,33,40,41). TIGAR is also regulated by NFB and PHD1 (42).…”

Section: Discussionmentioning

confidence: 99%

TP53-inducible Glycolysis and Apoptosis Regulator (TIGAR) Metabolically Reprograms Carcinoma and Stromal Cells in Breast Cancer

Ko¹,

Domingo‐Vidal²,

Roche³

et al. 2016

Journal of Biological Chemistry

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A subgroup of breast cancers has several metabolic compartments. The mechanisms by which metabolic compartmentalization develop in tumors are poorly characterized. TP53 inducible glycolysis and apoptosis regulator (TIGAR) is a bisphosphatase that reduces glycolysis and is highly expressed in carcinoma cells in the majority of human breast cancers. Hence we set out to determine the effects of TIGAR expression on breast carcinoma and fibroblast glycolytic phenotype and tumor growth. The overexpression of this bisphosphatase in carcinoma cells induces expression of enzymes and transporters involved in the catabolism of lactate and glutamine. Carcinoma cells overexpressing TIGAR have higher oxygen consumption rates and ATP levels when exposed to glutamine, lactate, or the combination of glutamine and lactate. Coculture of TIGAR overexpressing carcinoma cells and fibroblasts compared with control cocultures induce more pronounced glycolytic differences between carcinoma and fibroblast cells. Carcinoma cells overexpressing TIGAR have reduced glucose uptake and lactate production. Conversely, fibroblasts in coculture with TIGAR overexpressing carcinoma cells induce HIF (hypoxia-inducible factor) activation with increased glucose uptake, increased 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 (PFKFB3), and lactate dehydrogenase-A expression. We also studied the effect of this enzyme on tumor growth. TIGAR overexpression in carcinoma cells increases tumor growth in vivo with increased proliferation rates. However, a catalytically inactive variant of TIGAR did not induce tumor growth. Therefore, TIGAR expression in breast carcinoma cells promotes metabolic compartmentalization and tumor growth with a mitochondrial metabolic phenotype with lactate and glutamine catabolism. Targeting TIGAR warrants consideration as a potential therapy for breast cancer.

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“…Reactive oxygen species (ROS) are byproducts of oxygen metabolism, extensively and promptly generated in ischemic tissues after reperfusion [57][58][59][60] . ROS accumulation results in oxidative damage, opening of the mitochondrial permeability transition pore, and mitochondria-dependent cell death.…”

Section: Reactive Oxygen Speciesmentioning

confidence: 99%

Regulation of mitophagy in ischemic brain injury

et al. 2015

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The selective degradation of damaged or excessive mitochondria by autophagy is termed mitophagy. Mitophagy is crucial for mitochondrial quality control and has been implicated in several neurodegenerative disorders as well as in ischemic brain injury. Emerging evidence suggested that the role of mitophagy in cerebral ischemia may depend on different pathological processes. In particular, a neuroprotective role of mitophagy has been proposed, and the regulation of mitophagy seems to be important in cell survival. For these reasons, extensive investigations aimed to profile the mitophagy process and its underlying molecular mechanisms have been executed in recent years. In this review, we summarize the current knowledge regarding the mitophagy process and its role in cerebral ischemia, and focus on the pathological events and molecules that regulate mitophagy in ischemic brain injury.

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Ischemia/reperfusion-induced upregulation of TIGAR in brain is mediated by SP1 and modulated by ROS and hormones involved in glucose metabolism

Cited by 34 publications

References 39 publications

NADPH ameliorates MPTP-induced dopaminergic neurodegeneration through inhibiting p38MAPK activation

NADPH ameliorates MPTP-induced dopaminergic neurodegeneration through inhibiting p38MAPK activation

TP53-inducible Glycolysis and Apoptosis Regulator (TIGAR) Metabolically Reprograms Carcinoma and Stromal Cells in Breast Cancer

Regulation of mitophagy in ischemic brain injury

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