Characterization of cytosolic malic enzyme in human tumor cells

Loeber, Gerhard; Dworkin, Mark B.; Infante, Anthony A.; Ahorn, Horst

doi:10.1016/0014-5793(94)00386-6

Cited by 57 publications

(66 citation statements)

References 19 publications

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“…Thus, the progressive increase in ME mRNA found in our experiments may be due to an involvement of this enzyme in the microsomal biotransformation of drugs and the induction of its expression may be, therefore, a consequence of the cell requirement of reducing power against the oxidative stress. The increased expression of mRNA ME may also be relevant in producing pyruvate, which can be required in chronic diseases and in tumour cells (Loeber et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Malic enzyme and glucose 6-phosphate dehydrogenase gene expression increases in rat liver cirrhogenesis

Sanz

Dı́ez-Fernández²,

Valverde³

et al. 1997

Br J Cancer

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Summary The cirrhogenic ability of thioacetamide has been used to induce a model of chronic generalized liver disease that resembles the preneoplastic state of human fibrosis. Malic enzyme (ME) and glucose-6-phosphate dehydrogenase (G6PDH) are two cytosolic NADPHgenerating enzymes; their activities significantly increased in liver when macronodular cirrhosis was induced by long-term thioacetamide administration to rats. The progressive increase in G6PDH and ME activities during the cirrhogenic process is parallel to the induction in gene expression of both enzymes detected by the increase in their mRNAs. These data indicate that NADPH-consuming mechanisms such as the microsomal oxidizing system and the maintenance of the cell redox state could be involved. A relationship between the extent of G6PD and ME gene expression and oxidative stress generated by the oxidative metabolism of thioacetamide is proposed as the hepatic concentration of malondialdehyde, a metabolite derived from lipid peroxidation, underwent a progressive and significant enhancement during thioacetamide-induced cirrhogenesis. These results led us to suggest that the enhanced activities of G6PDH and ME might be related to microsomal mechanisms of detoxification as well as to the maintenance of the cellular redox state. Furthermore, the noticeable increase in the hepatocyte population involved in DNA replication parallel to G6PDH activity suggests that G6PDH, through ribose-5-phosphate, might also be involved in the processes of DNA synthesis and repair.

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Section: Discussionmentioning

confidence: 99%

Malic enzyme and glucose 6-phosphate dehydrogenase gene expression increases in rat liver cirrhogenesis

Sanz

Dı́ez-Fernández²,

Valverde³

et al. 1997

Br J Cancer

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“…3B). These distributions showed limited change when CT8/12, CT8, CT12, and CT20 were analyzed separately (39,30,51, and 44% up-regulated at CT8/12, CT8, CT12, and CT20, respectively). Because ID2 acts as a transcriptional repressor, this finding is surprising because one would expect most genes to be up-regulated in the absence of ID2.…”

Section: Id2 In Hepatic Circadian Clock Outputmentioning

confidence: 99%

ID2 (Inhibitor of DNA Binding 2) Is a Rhythmically Expressed Transcriptional Repressor Required for Circadian Clock Output in Mouse Liver

Hou

Ward

Murad

et al. 2009

Journal of Biological Chemistry

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Id2 is a helix-loop-helix transcription factor gene expressed in a circadian manner in multiple tissues with a phase-locked relationship with canonical clock genes (1). Our previous studies have identified circadian phenotypes in Id2 null mice, including enhanced photo-entrainment and disruption of activity rhythms, and have demonstrated a potent inhibitory effect of ID proteins upon CLOCK-BMAL1 transactivation of clock gene and clock-controlled gene activity (1). We have now begun to explore the potential role that ID2 may play in specifically regulating clock output. Here we show that ID2 protein is rhythmically expressed in mouse liver. Time-of-day-specific liver gene expression in Id2 ؉/؉ and Id2 ؊/؊ mice under circadian conditions was studied using DNA microarray analysis, identifying 651 differentially expressed genes, including a subset of 318 genes deemed rhythmically expressed in other studies. Examination of individual time courses reveals that these genes are dysregulated in a highly time-specific manner. A cohort of different functional groups were identified, including genes associated with glucose and lipid metabolism, e.g. serum protein Igfbp1 and lipoprotein lipase. We also reveal that the Id2 ؊/؊ mice show a reduction in lipid storage in the liver and white adipose tissue, suggesting that disruption of normal circadian activity of components of lipid metabolism can result in overt physiological alterations. These data reveal a role for the transcriptional repressor ID2 as a circadian output regulator in the periphery.Circadian rhythms are endogenous biochemical, physiological, and behavioral 24-h oscillations that persist under constant conditions and are generated by a series of intracellular transcriptional-translational feedback loops, composed of positive and negative components (2, 3). The positive loop consists of CLOCK (circadian locomotor output cycle kaput) and BMAL1

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“…Depending on the cofactor utilized, MEs can be classified as NAD ϩ dependent (EC 1.1.1.38 and EC 1.1.1.39; the latter is also able to decarboxylate OXA) or NADP ϩ dependent (EC 1.1.1.40). Different roles have been assigned to MEs in plants and mammals (7,16,23); however, little is known about the role of these enzymes in prokaryotes. In mammals, the relevance of cytosolic and mitochondrial NADP ϩ -dependent MEs is related to their ability to generate reduction equivalents for the biosynthesis of saturated fatty acids, while the human mitochondrial NAD ϩ -dependent ME is believed to play an important role in glutamine metabolism in fast-growing tissues and tumors (16,23).…”

mentioning

confidence: 99%

“…Different roles have been assigned to MEs in plants and mammals (7,16,23); however, little is known about the role of these enzymes in prokaryotes. In mammals, the relevance of cytosolic and mitochondrial NADP ϩ -dependent MEs is related to their ability to generate reduction equivalents for the biosynthesis of saturated fatty acids, while the human mitochondrial NAD ϩ -dependent ME is believed to play an important role in glutamine metabolism in fast-growing tissues and tumors (16,23). In plants, different MEs are involved in a wide range of metabolic pathways, such as the carbon flux of C 3 -C 4 intermediates between different organelles and in C 4 photosynthesis (7).…”

mentioning

confidence: 99%

Impact of Malic Enzymes on Antibiotic and Triacylglycerol Production in Streptomyces coelicolor

Rodrı́guez

Navone

Gramajo

2012

Appl Environ Microbiol

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ABSTRACTIn this paper, we have characterized two malic enzymes (ME), SCO2951 and SCO5261, fromStreptomyces coelicolorand analyzed their role in antibiotic and triacylglycerol (TAG) production. Biochemical studies have demonstrated that Sco2951 and Sco5261 genes encode NAD+- and NADP+-dependent malic enzymes, respectively. Single or double mutants in the ME-encoding genes show no effect on growth rate compared to the parental M145 strain. However, the single Sco2951 and the double Sco2951 Sco5261 mutants display a strong reduction in the production of the polyketide antibiotic actinorhodin; additionally, the Sco2951 Sco5261 mutant shows a decrease in stored TAGs during exponential growth. The lower production of actinorhodin in the double mutant occurs as a consequence of a decrease in the expression ofactII-ORF4, the transcriptional activator of the actinorhodin gene cluster. On the other hand, the reduced TAG accumulation is not due to reduced transcript levels of fatty acid biosynthetic genes nor to changes in the amount of the precursor acetyl coenzyme A (acetyl-CoA). This mutant accumulates intermediates of the tricarboxylic acid (TCA) cycle that could alter the regulation of the actinorhodin biosynthetic pathway, suggesting that MEs are important anaplerotic enzymes that redirect C4 intermediates from the TCA cycle to maintain secondary metabolism and TAG production inStreptomyces.

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Characterization of cytosolic malic enzyme in human tumor cells

Cited by 57 publications

References 19 publications

Malic enzyme and glucose 6-phosphate dehydrogenase gene expression increases in rat liver cirrhogenesis

Malic enzyme and glucose 6-phosphate dehydrogenase gene expression increases in rat liver cirrhogenesis

ID2 (Inhibitor of DNA Binding 2) Is a Rhythmically Expressed Transcriptional Repressor Required for Circadian Clock Output in Mouse Liver

Impact of Malic Enzymes on Antibiotic and Triacylglycerol Production in Streptomyces coelicolor

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