Induction of KLF4 contributes to the neurotoxicity of MPP + in M17 cells: a new implication in Parkinson's disease.
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.
Department of Neurology, Affiliated Hospital of Binzhou Medical College, No. 661, the 2nd Yellow River Road, Binzhou City, Shandong Province, 256603, China.
Jinbo
J
Chen
Xuezhen
X
Wang
Xiangming
X
Yi
Yuan
Y
Wang
Qingxin
Q
Liu
Ruli
R
Ge
D000447:Aldehydes / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020267:MPTP Poisoning / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress; D050050:Protein Carbonylation; D011726:Pyridinium Compounds / Q000633:toxicity*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1
D000447:Aldehydes; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D011726:Pyridinium Compounds; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; C026560:1-(4-methoxyphenyl)pyridinium; C547259:4-hydroperoxy-2-nonenal; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1