| Summary: | 碩士 === 臺北醫學大學 === 藥學系(碩博士班) === 102 === Previous studies have shown the accumulation of advanced glycation end products (AGEs) in neurodegeneration which is highly related to hypoxia. However, the relationship between AGEs and hypoxia is still unknown. Metformin, a well-known Type 2 DM drug, can work as AGEs inhibitors and is beneficial to neurons. In this study, we investigated the concentrations of one AGEs precursor, methylglyoxal (MG) in pheochromocytoma cells (PC12) under hypoxia condition. Furthermore, we also studied the effect of metformin on MG, its metabolite, D-lactate, L-lactate, and intracellular oxidative stress (total ROS). We chose to treat PC12 with 10 to 100 μM metformin and 5% oxygen for 24 hours. And then we investigated the effect of metformin (0, 10, 50, 100 μM ) on MG, its metabolite, D-lactate, L-lactate, and intracellular oxidative stress (total ROS) in PC12 with hypoxia treatment. The results indicated that, (1) In PC12 cells, hypoxia treatment can induce excessive intracellular MG accumulation (0.04 ± 0.03 vs. 0.28 ± 0.08, p < 0.01). (2) In PC12 cells, metformin (10, 50, 100 μM) can significantly suppress intracellular MG under hypoxia condition(0.28 ± 0.08 vs.0.14 ± 0.05, p < 0.01; 0.28 ± 0.08 vs.0.07 ± 0.02, p < 0.01; 0.28 ± 0.08 vs.0.10 ± 0.04, p < 0.01) (3) Hypoxia treatment cannot induce excessive intracellular D-lactate accumulation, and metformin treatment had no effect on it. (4) In PC12 cells, L-lactate showed increasing tendency under hypoxia condition,and metformin treatment did not make any effects. (5) In PC12 cells, metformin (10, 50 μM) can significantly suppress intracellular ROS under hypoxia condition (55.87 ± 12.64 vs. 35.83 ± 2.74, p < 0.05；55.87 ± 12.64 vs. 43.66 ± 2.45, p < 0.05).Only with 10 μM metformin treatment, intracellular ROS under hypoxia condition had no significant difference with normoxia condition.
As mentioned above, we found MG level had some relationship with intracellular ROS. Hence, though MG and D-Lactate may cause cell injury, cells were more vulnerable to MG accumulation under hypoxia condition.
In conclusion, in PC12, metformin can directly protect cell from hypoxia-induced MG accumulation, and lower metformin concentration was considered better choice.
Keywords: advanced glycation end products (AGEs), methylglyoxal (MG), hypoxia, pheochromocytoma cells (PC12), D-Lactate﹐metformin
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