title: Dopamine Release Suppression Dependent on an Increase of Intracellular Ca(2+) Contributed to Rotenone-induced Neurotoxicity in PC12 Cells.
abstract: Rotenone is an inhibitor of mitochondrial complex I that produces a model of Parkinson's disease (PD), in which neurons undergo dopamine release dysfunction and other features. In neurons, exocytosis is one of the processes associated with dopamine release and is dependent on Ca(2+) dynamic changes of the cell. In the present study, we have investigated the exocytosis of dopamine and the involvement of Ca(2+) in dopamine release in PC12 cells administrated with rotenone. Results demonstrated that rotenone led to an elevation of intracellular Ca(2+) through Ca(2+) influx by opening of the voltage-gated Ca(2+) channel and influenced the soluble N-ethylmaleimide attachment protein receptor (SNARE) proteins expression (including syntaxin, vesicle-associated membrane protein 2 (VAMP2) and synaptosome-associated protein 25 (SNAP-25)); pretreatment with a blocker of L-type voltage-activated Ca(2+) channels (nifedipine) decreased the intracellular dopamine levels and ROS formation, increased the cell viability and enhanced the neurite outgrowth and exocytosis of synaptic vesicles. These results indicated that the involvement of intracellular Ca(2+) was one of the factors resulting in suppression of dopamine release suppression in PC12 cells intoxicated with rotenone, which was associated with the rotenone-induced dopamine neurotoxicity.
authors.affiliation: Institute of Toxicology, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Sai
authors.forename: Junfeng
authors.initials: J
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Ye
authors.forename: Yuanpeng
authors.initials: Y
authors.lastname: Zhao
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zou
authors.forename: Jia
authors.initials: J
authors.lastname: Cao
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Dong
keywords: Ca2+; PC12 cells; dopamine release; neurotoxicity; rotenone
references.citation: Cell. 1999 Apr 16;97(2):165-74
references.pmid: 10219238
references.citation: Neuroscience. 2011 Dec 15;198:112-37
references.pmid: 21939738
references.citation: J Physiol. 2011 Apr 1;589(Pt 7):1603-18
references.pmid: 21282288
references.citation: J Cell Biol. 2008 Oct 20;183(2):323-37
references.pmid: 18936251
references.citation: Nat Struct Mol Biol. 2008 Jul;15(7):707-13
references.pmid: 18552825
references.citation: J Cell Mol Med. 2009 Oct;13(10):4161-5
references.pmid: 19737333
references.citation: Free Radic Biol Med. 2005 Jul 1;39(1):133-42
references.pmid: 15925285
references.citation: J Agromedicine. 2008;13(1):37-48
references.pmid: 19042691
references.citation: Neurobiol Dis. 2010 Oct;40(1):113-9
references.pmid: 20211259
references.citation: Biochem Biophys Res Commun. 2008 Sep 5;373(4):665-9
references.pmid: 18601902
references.citation: Toxicol In Vitro. 2008 Sep;22(6):1461-8
references.pmid: 18579341
references.citation: Neuron. 2003 Sep 11;39(6):889-909
references.pmid: 12971891
references.citation: Parkinsonism Relat Disord. 2003 Aug;9 Suppl 2:S59-64
references.pmid: 12915069
references.citation: J Neurosci. 2011 Feb 16;31(7):2421-30
references.pmid: 21325509
references.citation: J Cell Sci. 2010 Sep 15;123(Pt 18):3201-8
references.pmid: 20736314
references.citation: Neuron. 1999 Oct;24(2):363-76
references.pmid: 10571230
references.citation: Cell Calcium. 2008 Jan;43(1):9-15
references.pmid: 17382386
references.citation: Mol Cell. 2008 Jun 20;30(6):667-77
references.pmid: 18570870
references.citation: Methods Mol Biol. 2008;440:349-69
references.pmid: 18369958
references.citation: J Neurosci. 2010 Jul 21;30(29):9762-70
references.pmid: 20660258
references.citation: Nat Neurosci. 2000 Dec;3(12):1301-6
references.pmid: 11100151