Role of malate dehydrogenase in facilitating lactate dehydrogenase to support the glycolysis pathway in tumors

作者: Siavash Mansouri , Ali Shahriari , Hadi Kalantar , Taraneh Moini Zanjani , Mojtaba Haghi Karamallah

DOI: 10.3892/BR.2017.873

关键词: Anaerobic glycolysisMolecular biologyGlycolysisNicotinamide adenine dinucleotideEnzymeNAD+ kinaseMetabolismLactate dehydrogenaseBiologyBiochemistryMalate dehydrogenase

摘要: High aerobic glycolysis, as one of the hallmarks cancer cells, requires nicotinamide adenine dinucleotide (NAD+) a vital co-factor, to guarantee flow glycolysis. Malate dehydrogenase (MDH), an important enzyme in metabolism, is source NAD+ additional lactate (LDH). The current study aimed elucidate kinetic parameters MDH human breast and evaluate its supportive role glycolysis pathway. Michaelis-Menten constant (Km) maximum velocity (Vmax) were determined crude extracts tumors healthy tissue samples, which obtained directly from operating theatre. To assess potential supporting activity was measured when LDH inhibited by different concentrations oxamate, inhibitor cell lines. Km cancerous (C-MDH) same MDH, although Vmax C-MDH higher relative MDH. Notably, increased MDA-MB-231 line, treated with (oxamate), but not MCF-7 line (P<0.05). tendency for malate generation cells effective approach Increasing absence demonstrates Therefore, decreasing expression forward reaction may present valid molecular target abolish effect on tumor metabolism.

参考文章(23)
S. P. J. Brooks, A program for analyzing enzyme rate data obtained from a microplate reader. BioTechniques. ,vol. 17, pp. 1154- 1161 ,(1994)
Kenneth B. Storey, Stephen P.J. Brooks, Chapter 6 The basis of enzymatic adaptation Principles of Medical Biology. ,vol. 4, pp. 147- 169 ,(1995) , 10.1016/S1569-2582(06)80008-5
Doris Balinsky, Charles E. Platz, Jeffrey W. Lewis, Isozyme Patterns of Normal, Benign, and Malignant Human Breast Tissues Cancer Research. ,vol. 43, pp. 5895- 5901 ,(1983)
Francesco Belfiore, Vito Borzi, Luigi Lo Vecchio, Elena Napoli, Agata M Rabuazzo, Enzyme Activities of NADPH-Forming Metabolic Pathways in Normal and Leukemic Leukocytes Clinical Chemistry. ,vol. 21, pp. 880- 883 ,(1975) , 10.1093/CLINCHEM/21.7.880
M B Grisham, L H Bernstein, J Everse, The cytoplasmic malate dehydrogenase in neoplastic tissues; presence of a novel isoenzyme? British Journal of Cancer. ,vol. 47, pp. 727- 731 ,(1983) , 10.1038/BJC.1983.113
Dai Fukumura, Rakesh K. Jain, Tumor microenvironment abnormalities: Causes, consequences, and strategies to normalize Journal of Cellular Biochemistry. ,vol. 101, pp. 937- 949 ,(2007) , 10.1002/JCB.21187
Ralph J. DeBerardinis, Julian J. Lum, Georgia Hatzivassiliou, Craig B. Thompson, THE BIOLOGY OF CANCER: METABOLIC REPROGRAMMING FUELS CELL GROWTH AND PROLIFERATION Cell Metabolism. ,vol. 7, pp. 11- 20 ,(2008) , 10.1016/J.CMET.2007.10.002
Michael I. Koukourakis, Emmanuel Kontomanolis, Alexandra Giatromanolaki, Efthimios Sivridis, Vassilios Liberis, Serum and Tissue LDH Levels in Patients with Breast/Gynaecological Cancer and Benign Diseases Gynecologic and Obstetric Investigation. ,vol. 67, pp. 162- 168 ,(2009) , 10.1159/000183250
Rob A. Cairns, Isaac S. Harris, Tak W. Mak, Regulation of cancer cell metabolism Nature Reviews Cancer. ,vol. 11, pp. 85- 95 ,(2011) , 10.1038/NRC2981
Michael I. Koukourakis, Alexandra Giatromanolaki, Stuart Winter, Russel Leek, Efthimios Sivridis, Adrian L. Harris, Lactate dehydrogenase 5 expression in squamous cell head and neck cancer relates to prognosis following radical or postoperative radiotherapy. Oncology. ,vol. 77, pp. 285- 292 ,(2009) , 10.1159/000259260