Differential expression of phosphofructokinase-1 isoforms correlates with the glycolytic efficiency of breast cancer cells

Zancan, Patrícia; Sola‐Penna, Mauro; Furtado, Cristiane M.; Silva, Daniel da

doi:10.1016/j.ymgme.2010.04.006

Cited by 93 publications

(71 citation statements)

References 43 publications

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“…The association of glycolytic enzymes to these intracellular ultrastructures is an important mechanism of regulation of glucose consumption, determining if it will be completely oxidized, fermented, or used as carbon source for biosynthesis (17,19,20,22,36,(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53). The more associated the enzymes are, the less oxidized glucose is, being preferentially fermented and used to biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Metformin reverses hexokinase and phosphofructokinase downregulation and intracellular distribution in the heart of diabetic mice

Silva¹,

Ausina²,

Alencar³

et al. 2012

IUBMB Life

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SummaryDiabetes mellitus is characterized by hyperglycemia and its associated complications, including cardiomyopathy. Metformin, in addition to lowering blood glucose levels, provides cardioprotection for diabetic subjects. Glycolysis is essential to cardiac metabolism and its reduction may contribute to diabetic cardiomyopathy. Hexokinase (HK) and phosphofructokinase (PFK), rate-limiting enzymes of glycolysis, are downregulated in cardiac muscle from diabetic subjects, playing a central role on the decreased glucose utilization in the heart of diabetic subjects. Thus, the aim of this study was to determine whether metformin modulates heart HK and PFK from diabetic mice. Diabetes was induced by streptozotocin injection on male Swiss mice, which were treated for three consecutive days with 250 mg/kg metformin before evaluating HK and PFK activity, expression, and intracellular distribution on the heart of these subjects. We show that metformin abrogates the downregulation of HK and PFK in the heart of streptozotocin-induced diabetic mice. This effect is not correlated to alteration on the enzymes' transcription and expression. However, the intracellular distribution of both enzymes is altered in diabetic hearts that show increased activity of the soluble fraction when compared to the particulate fraction. Moreover, this pattern is reversed upon the treatment with metformin, which is correlated with the effects of the drug on the enzymes activity. Altogether, our results support evidences that metformin alter the intracellular localization of HK and PFK augmenting glucose utilization by diabetic hearts and, thus, conferring cardiac protection to diabetic subjects.

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Section: Discussionmentioning

confidence: 99%

Metformin reverses hexokinase and phosphofructokinase downregulation and intracellular distribution in the heart of diabetic mice

Silva¹,

Ausina²,

Alencar³

et al. 2012

IUBMB Life

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“…Cells of the breast cancer cell line, MDA-MB-231, also express a high level of hexokinase II (Furtado et al, 2012;Zancan et al, 2010). As shown in (Fig.…”

Section: Sirt-3 Modulates Loss Of Cell Viability Induced By Mcl-1 Andmentioning

confidence: 91%

Sirtuin-3 modulates Bak- and Bax-dependent apoptosis

Verma

Shulga

Pastorino

2013

Journal of Cell Science

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SummarySirtuin-3 exhibits properties of a tumor suppressor partly emanating from its ability to control the state of mitochondrial metabolism, with depletion of sirt-3 increasing tumor cell survival. In the present study we demonstrate that depletion of sirtuin-3 brings about an anti-apoptotic phenotype via stimulating cyclophilin-D activity, which promotes the binding of hexokinase II to the mitochondria, thereby preventing Bak/Bax dependent mitochondrial injury and cell death. By contrast, increased expression of sirtuin-3 decreases cyclophilin-D activity, resulting in detachment of hexokinase II from the mitochondria and potentiation of Bak-and Bax-induced mitochondrial injury and loss of cell viability.

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“…These include glucose transporters (GLUT1, GLUT3), glycolytic enzymes (HKI, HKII, PFK-1, ALDO-A, ALDO-C, PGK1, ENO-a, PK-M2, PFKFB-3) and enzymes related to lactate production and lactate/proton extrusion (LDH-A, MCT4). 33,34 Hypoxia also induces the expression of the pyruvate dehydrogenase kinases (PDK1 and PDK3 isoforms), 26,35 which have different activities and specificities for the phosphorylation and inactivation of the three isoforms of pyruvate dehydrogenases (PDHA1, PDHA2 and PDHB), 36,37 which transform pyruvate into acetyl-CoA (Fig. 2).…”

Section: Tumor Cell Metabolism In Hypoxic and Normoxic Conditionsmentioning

confidence: 99%

“…75 In contrast, PFK-1 activity is significantly increased in cancer cell lines and primary tumor tissues. 34,62 The p53-inducible TIGAR protein, aside from promoting PPP, helps to lower intracellular ROS levels. 95 Glucose is also the main precursor for R5P synthesis in tumor cells; more than 90% of ribose molecules have been shown to be glucose-derived in the H441 lung tumor cell line.…”

Section: Tumor Cells Synthesize Fatty Acids and Nucleotides At High Rmentioning

confidence: 99%

Tumor cell metabolism

Romero-García

López‐González

Báez-Viveros

et al. 2011

Cancer Biology & Therapy

192

118

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Differential expression of phosphofructokinase-1 isoforms correlates with the glycolytic efficiency of breast cancer cells

Cited by 93 publications

References 43 publications

Metformin reverses hexokinase and phosphofructokinase downregulation and intracellular distribution in the heart of diabetic mice

Metformin reverses hexokinase and phosphofructokinase downregulation and intracellular distribution in the heart of diabetic mice

Sirtuin-3 modulates Bak- and Bax-dependent apoptosis

Tumor cell metabolism

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