Jain S K, Morshed K M, Kannan K, McMartin K E, Bocchini J A
Department of Pediatrics, Louisiana State University School of Medicine, Shreveport 71130, USA.
Mol Cell Biochem. 1996 Sep 6;162(1):11-6. doi: 10.1007/BF00250990.
This study has examined whether elevated glucose can induce lipid peroxidation and contribute to the inhibition of cell growth in human kidney proximal tubule(HPT) cells. HPT cells were cultured in media containing glucose concentrations of 8 mM (control), 25 mM, and 50 mM. Lipid peroxidation was assessed by the thiobarbituric acid reactivity and cell growth was assessed by 3H-thymidine uptake. Results show decreased (59%, p < 0.01) growth of HPT cells cultured in 50 mM glucose. Cells cultured in 50 mM mannitol did not show any growth inhibition, suggesting that the decreased cell growth associated with glucose is not due to osmolarity changes. There was an increase (108%, p < 0.02) in lipid peroxidation in cells cultured with high levels of glucose (50 mM) compared with controls and cells cultured with 50 mM mannitol. To examine if membrane lipid peroxidation or malondialdehyde (MDA, an end product of lipid peroxidation) has any role in the inhibition of cell growth, we examined the effect of tertiary butylhydroperoxide (TBH, known to cause lipid peroxidation and generate MDA) on the growth of HPT cells. TBH decreased cell growth (49, 17 and 3% of controls at 0.1, 0.25, and 0.5 mumole TBH/ml medium). Similarly, a marked reduction in the growth was observed with exogenous MDA (72, 69 and 34% of controls at 0.1, 0.25, and 0.5 mumole MDA/ml medium). This suggests that elevated glucose can induce membrane lipid peroxidation and accumulation of MDA, which in turn can inhibit cellular growth and contribute to the altered structure and function of HPT cells in diabetes.
本研究检测了高糖是否会诱导脂质过氧化并导致人肾近端小管（HPT）细胞生长受抑制。将HPT细胞培养于含8 mM（对照）、25 mM和50 mM葡萄糖浓度的培养基中。通过硫代巴比妥酸反应性评估脂质过氧化，通过3H-胸腺嘧啶核苷摄取评估细胞生长。结果显示，在50 mM葡萄糖中培养的HPT细胞生长下降（59%，p < 0.01）。在50 mM甘露醇中培养的细胞未表现出任何生长抑制，这表明与葡萄糖相关的细胞生长下降并非由于渗透压变化。与对照组及在50 mM甘露醇中培养的细胞相比，在高糖（50 mM）中培养的细胞脂质过氧化增加（108%，p < 0.02）。为检测膜脂质过氧化或丙二醛（MDA，脂质过氧化的终产物）是否在细胞生长抑制中起作用，我们检测了叔丁基过氧化氢（TBH，已知可引起脂质过氧化并生成MDA）对HPT细胞生长的影响。TBH使细胞生长下降（在0.1、0.25和0.5 μmol TBH/ml培养基中分别为对照组的49%、17%和3%）。同样，外源性MDA也使生长显著降低（在0.1、0.25和0.5 μmol MDA/ml培养基中分别为对照组的72%、69%和34%）。这表明高糖可诱导膜脂质过氧化和MDA积累，进而抑制细胞生长，并导致糖尿病状态下HPT细胞结构和功能改变。
