Department of Neurology, Affiliated Hospital of Binzhou Medical College, No. 661, the 2nd Yellow River Road, Binzhou City, Shandong Province, 256603, China.
J Mol Neurosci. 2013 Sep;51(1):109-17. doi: 10.1007/s12031-013-9961-3. Epub 2013 Feb 1.
Parkinson's disease (PD) is the second most common neurodegenerative disease in humans. The effect of Krüppel-like factor (KLF) 4 in PD is unknown. In this study, KLF4 was found to be increased in both a time-dependent manner and a dose-dependent manner in response to the incubation with 1-methyl-4-phenylpyridinium (MPP+) in human dopamine neuroblastoma M17 cells, suggesting a potential role in MPP + -induced neurotoxicity. Following experiments showed that overexpression of KLF4 in M17 cells promoted MPP + -induced oxidative stress, embodied by exacerbated reactive oxygen species, 4-hydroxy-2-nonenal, and protein carbonyls. Furthermore, overexpression of KLF4 slowed cell proliferation and promoted lactate dehydrogenase release. Conversely, inhibition of KLF4 in M17 cells attenuated MPP + -induced neurotoxicity. The expression of superoxide dismutase (SOD) 1 in both mRNA and protein levels was found to be decreased by overexpressing KLF4, while increased by knockdown of KLF4. Moreover, promoter luciferase experiments showed that transcriptional activity on SOD1 was inhibited by KLF4. All the results indicated that KLF4 promoted the neurotoxicity of MPP + via inhibiting the transcription of SOD1, suggesting a potential mechanism of increased oxidative stress and cell death in Parkinson's disease.
帕金森病（PD）是人类第二常见的神经退行性疾病。Krüppel 样因子（KLF）4 在 PD 中的作用尚不清楚。在这项研究中，发现人多巴胺神经母细胞瘤 M17 细胞孵育 1-甲基-4-苯基吡啶（MPP+）后，KLF4 呈时间依赖性和剂量依赖性增加，提示其在 MPP +诱导的神经毒性中可能起作用。后续实验表明，在 M17 细胞中过表达 KLF4 会促进 MPP +诱导的氧化应激，表现为活性氧、4-羟基-2-壬烯醛和蛋白质羰基的加剧。此外，KLF4 的过表达会减缓细胞增殖并促进乳酸脱氢酶释放。相反，在 M17 细胞中抑制 KLF4 会减轻 MPP +诱导的神经毒性。结果发现，过表达 KLF4 会降低 SOD1 的 mRNA 和蛋白水平表达，而敲低 KLF4 则会增加 SOD1 的表达。此外，启动子荧光素酶实验表明，KLF4 抑制 SOD1 的转录活性。所有结果表明，KLF4 通过抑制 SOD1 的转录促进 MPP +的神经毒性，提示在帕金森病中氧化应激和细胞死亡增加的潜在机制。
