Functional Roles of Mitochondrial NAD(P)+-Dependent-Malic Enzyme (ME2) Lung and Breast Cancer Cell Line

• Main Authors: YA YU LU, 呂亞諭
• Other Authors: Hui-Chih Hung
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/52524676675814439583

碩士 === 國立中興大學 === 生命科學系所 === 101 === Malic enzyme (Malic Enzyme; ME) has three isoforms, which mitochondrial malic enzyme (Mitochondrial NAD (P) +-dependent malic enzyme; ME2) acting on the rapid proliferation of tissue, intestinal mucosa, spleen, thymus and tumor cells; ME2 catalytic substrates malate (Malate) generate pyruvate (Pyruvate), accompanied produce NADH. NADH in the mitochondrial membrane electron transport chain via oxidative phosphorylation to produce ATP provides direct role in cellular energy, the process will have a chance to produce O2-, via Superoxide Dismutase (SOD) catalyzes the formation of H2O2. Finally, to assist the formation of metal ions OH-, on the cell undergoes oxidation damage, thus activating downstream proteins, the occurrence of procedural plans death (Apoptosis). ME2 catalytic reaction accompanied by NADH generated energy metabolism as a major source of ATP molecules, while in the fight against ROS damage may also play a very important role in helping to generate and promote NADPH Glutathione (GSH) maintained at reduced state, effectively reduce the ROS injury. In the anticancer mechanism, in addition to promote apoptosis in cancer cells, but also inhibit the proliferation of channels, I also conducted research there for mitochondrial malic enzyme (Malic enzyme 2, ME2) mechanism for cell proliferation mitochondrial malic enzyme activity is correlated mitochondrial malic enzyme is a cell in another to obtain energy pathways, many tumor cells can use glutamine (glutamine) to replace glucose as a major energy source, malic enzyme ie the catalytic glutamate metabolism, called "Glutaminolysis". Metabolic process, α-ketoglutarate converted to malate system by the Krebs cycle (citric acid cycle) in enzyme catalysis. Normal intracellular malic acid in the Krebs cycle by malate dehydrogenase (malate dehydrogenase) catalysis of oxaloacetate; But in Glutaminolysis process, malic acid from malic enzyme catalyzed the formation of pyruvic acid (pyruvate). In the citric acid cycle malic acid (Malate) will be converted into the catalysis by ME2 pyruvate and NADH accompanied by the generation of carbon dioxide, the cells get energy and to promote cell proliferation. In addition, the majority of cancer cells generated from the epidermis, so epidermal growth factor EGF in cancer compared to other growth factors most universal and most research potential, but also found that ATP can induce increased activity of EGFR, suggesting that EGF and ME2 has the possibility of mutual influence. Then explore the ME2 in H1299 lung cancer cells (non-small cell lung cancer) than in normal lung cells whether overexpression, and overexpression of whether ME2 AKT/PI3K signaling pathway can be activated with the ERK / MAPK signaling pathway to induce cell proliferation; even after can be contacted by Repamycin (mTOR inhibitor) to investigate the activation of EGF and ME2 path, further research H1299 lung cancer cell proliferation inhibition ways.