Parkinson's disease (PD) is a common degenerative disease of the nervous system. The pathogenesis of PD is not yet clear. However, it has been reported that many factors including age, environmental factors, and genetic factors are included. Rotenone is one of the naturally occurring insecticides found in many plants of the Derris, Lonchocarpus, Tephrosia and Mundulea species. It is also one of the classic neurotoxic drugs to produce PD models. Ndfip1 has been reported to be a neuroprotective protein in the brain. Therefore, in this study, we examined the expression of Ndfip1 in the mitochondrial complex I inhibitor rotenone-induced PD models in MES23.5 dopaminergic cells. Our results showed that rotenone has a concentration-dependent and time-dependent impairment effect on MES23.5 cells. When the concentration of rotenone was 25 nmol/L, the viability of the cells was significantly decreased at 24 hrs. Further study showed that the expression of Ndfip1 increased in the mRNA levels at 6 hrs after 25 nmol/L rotenone treatment. The protein levels of Ndfip1 increased at 3 hrs, 6 hrs and decreased at 12 hrs after 100 nmol/L rotenone treatment. This indicates that rotenone caused damage to MES23.5 dopaminergic cells, which is accompanied by a decrease of Ndfip1.
Parkinson’ Disease, MES23.5 Cells, Rotenone, Ndfip1
- Jankovic, J., Parkinson's disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry, 2008. 79(4): p. 368-76.
- Halliwell, B., Reactive oxygen species and the central nervous system. J Neurochem, 1992. 59(5): p. 1609-23.
- Lee, V.M. and J.Q. Trojanowski, Mechanisms of Parkinson's disease linked to pathological alpha-synuclein: new targets for drug discovery. Neuron, 2006. 52(1): p. 33-8.
- Lin, M.T. and M.F. Beal, Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature, 2006. 443(7113): p. 787-95.
- Takahashi, R., J. Kawamata, and H. Takeuchi, [Pathogenesis of sporadic Parkinson's disease: contribution of genetic and environmental risk factors]. Rinsho Shinkeigaku, 2009. 49(11): p. 885-7.
- Zecca, L., et al., Iron, brain ageing and neurodegenerative disorders. Nat Rev Neurosci, 2004. 5(11): p. 863-73.
- Zhang, Y., V.L. Dawson, and T.M. Dawson, Oxidative stress and genetics in the pathogenesis of Parkinson's disease. Neurobiol Dis, 2000. 7(4): p. 240-50.
- Uversky, V.N., Neurotoxicant-induced animal models of Parkinson's disease: understanding the role of rotenone, maneb and paraquat in neurodegeneration. Cell Tissue Res, 2004. 318(1): p. 225-41.
- Betarbet, R., et al., Chronic systemic pesticide exposure reproduces features of Parkinson's disease. Nat Neurosci, 2000. 3(12): p. 1301-6.
- Manning-Bog, A.B., et al., The herbicide paraquat causes up-regulation and aggregation of alpha-synuclein in mice: paraquat and alpha-synuclein. J Biol Chem, 2002. 277(3): p. 1641-4.
- Seniuk, N.A., W.G. Tatton, and C.E. Greenwood, Dose-dependent destruction of the coeruleus-cortical and nigral-striatal projections by MPTP. Brain Res, 1990. 527(1): p. 7-20.
- Schapira, A.H., et al., Mitochondrial complex I deficiency in Parkinson's disease. J Neurochem, 1990. 54(3): p. 823-7.
- Jolliffe, C.N., et al., Identification of multiple proteins expressed in murine embryos as binding partners for the WW domains of the ubiquitin-protein ligase Nedd4. Biochem J, 2000. 351 Pt 3: p. 557-65.
- Harvey, K.F., et al., N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein. J Biol Chem, 2002. 277(11): p. 9307-17.
- Sang, Q., et al., Nedd4-WW domain-binding protein 5 (Ndfip1) is associated with neuronal survival after acute cortical brain injury. J Neurosci, 2006. 26(27): p. 7234-44.
- Xiong, N., et al., Mitochondrial complex I inhibitor rotenone-induced toxicity and its potential mechanisms in Parkinson's disease models. Crit Rev Toxicol, 2012. 42(7): p. 613-32.
- Sherer, T.B., et al., Mechanism of toxicity in rotenone models of Parkinson's disease. J Neurosci, 2003. 23(34): p. 10756-64.
- Domingues, H.S., et al., Oligodendrocyte, Astrocyte, and Microglia Crosstalk in Myelin Development, Damage, and Repair. Front Cell Dev Biol, 2016. 4: p. 71.
- Panov, A., et al., Rotenone model of Parkinson disease: multiple brain mitochondria dysfunctions after short term systemic rotenone intoxication. J Biol Chem, 2005. 280(51): p. 42026-35.
- Garcia-Garcia, F., et al., Sleep disturbances in the rotenone animal model of Parkinson disease. Brain Res, 2005. 1042(2): p. 160-8.
- Sherer, T.B., et al., An in vitro model of Parkinson's disease: linking mitochondrial impairment to altered alpha-synuclein metabolism and oxidative damage. J Neurosci, 2002. 22(16): p. 7006-15.
- Liu, L., et al., Oxidative stress contributes to arsenic-induced telomere attrition, chromosome instability, and apoptosis. J Biol Chem, 2003. 278(34): p. 31998-2004.
- Schuler, F. and J.E. Casida, Functional coupling of PSST and ND1 subunits in NADH:ubiquinone oxidoreductase established by photoaffinity labeling. Biochim Biophys Acta, 2001. 1506(1): p. 79-87.
- Ferrante, R.J., et al., Systemic administration of rotenone produces selective damage in the striatum and globus pallidus, but not in the substantia nigra. Brain Res, 1997. 753(1): p. 157-62.
- Howitt, J., et al., Ndfip1 regulates nuclear Pten import in vivo to promote neuronal survival following cerebral ischemia. J Cell Biol, 2012. 196(1): p. 29-36.
- Lackovic, J., et al., Differential regulation of Nedd4 ubiquitin ligases and their adaptor protein Ndfip1 in a rat model of ischemic stroke. Exp Neurol, 2012. 235(1): p. 326-35.
- Low, L.H., et al., Nedd4 family interacting protein 1 (Ndfip1) is required for ubiquitination and nuclear trafficking of BRCA1-associated ATM activator 1 (BRAT1) during the DNA damage response. J Biol Chem, 2015. 290(11): p. 7141-50.
- Liu, K., et al., Protective effects of Ndfip1 on MPP(+)-induced apoptosis in MES23.5 cells and its underlying mechanisms. Exp Neurol, 2015. 273: p. 215-24.
- Myat, A., et al., Drosophila Nedd4, a ubiquitin ligase, is recruited by Commissureless to control cell surface levels of the roundabout receptor. Neuron, 2002. 35(3): p. 447-59.
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