Prostaglandin A1 inhibits rotenone-induced apoptosis in SH-SY5Y cells

被引:78
作者
Wang, XX
Qin, ZH
Leng, Y
Wang, YM
Jin, XN
Chase, TN
Bennett, MC
机构
[1] NINDS, Expt Therapeut Branch, Bethesda, MD 20892 USA
[2] Massachusetts Gen Hosp, Boston, MA 02114 USA
[3] Harvard Univ, Sch Med, Lab Cellular & Neurobiol, Boston, MA USA
[4] Walter Reed Army Inst Res, Dept Biol, Div Expt Therapeut, Silver Spring, MD USA
[5] Blanchette Rockefeller Neurosci Inst, Rockville, MD USA
关键词
caspase-3; dopaminergic cell; mitochondrial complex I; nuclear factor-kappa B; Parkinson's disease; prostaglandin A1;
D O I
10.1046/j.1471-4159.2002.01224.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The degeneration of nigral dopamine neurons in Parkinson's disease (PD) reportedly involves a defect in brain mitochondrial complex I in association with the activation of nuclear factor-kappaB (NF-kappaB) and caspase-3. To elucidate molecular mechanisms possibly linking these events, as well as to evaluate the neuroprotective potential of the cyclopentenone prostaglandin A(1) (PGA(1)), an inducer of heat shock proteins (HSPs), we exposed human dopaminergic SH-SY5Y cells to the complex I inhibitor rotenone. Dose-dependent apoptosis was preceded by the nuclear translocation of NF-kappaB and then the activation of caspase-3 over the ensuing 24 h. PGA(1) increased the expression of HSP70 and HSP27 and protected against rotenone-induced apoptosis, without increasing necrotic death. PGA(1) blocked the rotenone-induced nuclear translocation of NF-kappaB and attenuated, but did not abolish, the caspase-3 elevation. Unexpectedly, the caspase-3 inhibitor, Ac-DEVD.CHO (DEVD), at a concentration that completely prevented the caspase-3 elevation produced by rotenone, failed to protect against apoptosis. These results suggest that complex I deficiency in dopamine cells can induce apoptosis by a process involving early NF-kappaB nuclear translocation and caspase-3 activation. PGA, appears to protect against rotenone-induced cell death by inducing HSPs and blocking nuclear translocation of NF-kappaB in a process that attenuates caspase-3 activation, but is not mediated by its inhibition.
引用
收藏
页码:1094 / 1102
页数:9
相关论文
共 49 条
[1]   Chaperone suppression of α-synuclein toxicity in a Drosophila model for Parkinson's disease [J].
Auluck, PK ;
Chan, HYE ;
Trojanowski, JQ ;
Lee, VMY ;
Bonini, NM .
SCIENCE, 2002, 295 (5556) :865-868
[2]   Control of apoptosis by Rel/NF-κB transcription factors [J].
Barkett, M ;
Gilmore, TD .
ONCOGENE, 1999, 18 (49) :6910-6924
[3]  
BIEDLER JL, 1978, CANCER RES, V38, P3751
[4]   Activation of the nuclear factor-κB is a key event in brain tolerance [J].
Blondeau, N ;
Widmann, C ;
Lazdunski, M ;
Heurteaux, C .
JOURNAL OF NEUROSCIENCE, 2001, 21 (13) :4668-4677
[5]   Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson's disease [J].
Blum, D ;
Torch, S ;
Lambeng, N ;
Nissou, MF ;
Benabid, AL ;
Sadoul, R ;
Verna, JM .
PROGRESS IN NEUROBIOLOGY, 2001, 65 (02) :135-172
[6]  
Blum JD, 2000, J HIGH ENERGY PHYS
[7]   Activation of nuclear factor κB and bcl-x survival gene expression by nerve growth factor requires tyrosine phosphorylation of IκBα [J].
Bui, NT ;
Livolsi, A ;
Peyron, JF ;
Prehn, JHM .
JOURNAL OF CELL BIOLOGY, 2001, 152 (04) :753-763
[8]   Interaction among mitochondria, mitogen-activated protein kinases, and nuclear factor-κB in cellular models of Parkinson's disease [J].
Cassarino, DS ;
Halvorsen, EM ;
Swerdlow, RH ;
Abramova, NN ;
Parker, WD ;
Sturgill, TW ;
Bennett, JP .
JOURNAL OF NEUROCHEMISTRY, 2000, 74 (04) :1384-1392
[9]   Dual role of the NF-κB transcription factor in the death of immature neurons [J].
Castagné, V ;
Lefévre, K ;
Clarke, PGH .
NEUROSCIENCE, 2001, 108 (03) :517-526
[10]   BIOLOGICAL AND CLINICAL IMPLICATIONS OF HEAT-SHOCK PROTEIN 27000 (HSP27) - A REVIEW [J].
CIOCCA, DR ;
OESTERREICH, S ;
CHAMNESS, GC ;
MCGUIRE, WL ;
FUQUA, SAW .
JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1993, 85 (19) :1558-1570