EurekaMag.com logo
+ Site Statistics
References:
53,869,633
Abstracts:
29,686,251
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on LinkedInFollow on LinkedIn

+ Translate

Environmental neurotoxin dieldrin induces apoptosis via caspase-3-dependent proteolytic activation of protein kinase C delta (PKCdelta): Implications for neurodegeneration in Parkinson's disease



Environmental neurotoxin dieldrin induces apoptosis via caspase-3-dependent proteolytic activation of protein kinase C delta (PKCdelta): Implications for neurodegeneration in Parkinson's disease



Molecular Brain 1(): 12-12



In previous work, we investigated dieldrin cytotoxicity and signaling cell death mechanisms in dopaminergic PC12 cells. Dieldrin has been reported to be one of the environmental factors correlated with Parkinson's disease and may selectively destroy dopaminergic neurons. Here we further investigated dieldrin toxicity in a dopaminergic neuronal cell model of Parkinson's disease, namely N27 cells, using biochemical, immunochemical, and flow cytometric analyses. In this study, dieldrin-treated N27 cells underwent a rapid and significant increase in reactive oxygen species followed by cytochrome c release into cytosol. The cytosolic cytochrome c activated caspase-dependent apoptotic pathway and the increased caspase-3 activity was observed following a 3 hr dieldrin exposure in a dose-dependent manner. Furthermore, dieldrin caused the caspase-dependent proteolytic cleavage of protein kinase C delta (PKCδ) into 41 kDa catalytic and 38 kDa regulatory subunits in N27 cells as well as in brain slices. PKCδ plays a critical role in executing the apoptotic process in dieldrin-treated dopaminergic neuronal cells because pretreatment with the PKCδ inhibitor rottlerin, or transfection and over-expression of catalytically inactive PKCδ(K)³⁷⁶(R), significantly attenuates dieldrin-induced DNA fragmentation and chromatin condensation. Together, we conclude that caspase-3-dependent proteolytic activation of PKCδ is a critical event in dieldrin-induced apoptotic cell death in dopaminergic neuronal cells.

(PDF emailed within 0-6 h: $19.90)

Accession: 052999486

Download citation: RISBibTeXText

PMID: 18945348

DOI: 10.1186/1756-6606-1-12



Related references

Chronic low-dose oxidative stress induces caspase-3-dependent PKCdelta proteolytic activation and apoptosis in a cell culture model of dopaminergic neurodegeneration. Annals of the New York Academy of Sciences 1139: 197-205, 2008

Tyrosine kinase inhibition attenuates oxidative stress induced caspase - 3 dependent proteolytic activation of PKCdelta and apoptosis in dopaminergic cells implications for oxidative stress signaling in parkinsons disease. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 233 5, 2003

Proteolytic activation of proapoptotic kinase PKCdelta is regulated by overexpression of Bcl-2: implications for oxidative stress and environmental factors in Parkinson's disease. Annals of the New York Academy of Sciences 1010: 683-686, 2004

Low dose oxidative insult promotes apoptosis in dopaminergic cells via caspase-3 dependent proteolytic activation of PKCdelta Relevance to environmental factors and Parkinsons disease. Toxicological Sciences 72(S-1): 79, March, 2003

Dieldrin induces caspase-3 dependent proteolytic cleavage of protein kinase Cdelta in dopaminergic cells relevance to etiopathogenesis of Parkinsons disease. Society for Neuroscience Abstracts 26(1-2): Abstract No -667 21, 2000

Dieldrin induces apoptosis by promoting caspase-3-dependent proteolytic cleavage of protein kinase Cdelta in dopaminergic cells: relevance to oxidative stress and dopaminergic degeneration. Neuroscience 119(4): 945-964, 2003

Involvement of protein kinase C delta (PKCdelta) in phorbol ester-induced apoptosis in LNCaP prostate cancer cells. Lack of proteolytic cleavage of PKCdelta. Journal of Biological Chemistry 275(11): 7574-7582, 2000

Chronic Low-Dose Oxidative Stress Induces Caspase-3-Dependent PKC Proteolytic Activation and Apoptosis in a Cell Culture Model of Dopaminergic Neurodegeneration. Annals of the New York Academy of Sciences 1139(none): 197-205, 2008

A novel peptide inhibitor targeted to caspase-3 cleavage site of a proapoptotic kinase protein kinase C delta (PKCdelta) protects against dopaminergic neuronal degeneration in Parkinson's disease models. Free Radical Biology & Medicine 41(10): 1578-1589, 2006

Activation of caspase-12 and upregulation of parkin protein during dopaminergic cell death induced by a Parkinsons disease-related environmental neurotoxin, dieldrin. Society for Neuroscience Abstracts 27(1): 516, 2001

Neuroprotective effect of alpha-synuclein involves attenuation of caspase-3 dependent proteolytic activation of PKCdelta in MPP+-induced apoptosis. Neurotoxicology (Little Rock) 24(2): 303-304, March, 2003

Proteolytic activation of protein kinase C delta and epsilon by caspase-3 in U937 cells during chemotherapeutic agent-induced apoptosis. Cellular Signalling 11(11): 831-838, 2000

Proteolytic activation of protein kinase C delta by an ICE/CED 3-like protease induces characteristics of apoptosis. Journal of Experimental Medicine 184(6): 2399-2404, 1996

Suppression of caspase-3-dependent proteolytic activation of protein kinase C delta by small interfering RNA prevents MPP+-induced dopaminergic degeneration. Molecular and Cellular Neurosciences 25(3): 406-421, 2004

D6-Hydroxydopamine- induced apoptosis is mediated via extracellular auto-oxidation and caspase 3-dependent activation of protein kinase C delta. Journal of Biological Chemistry 281(9): 5373-5382, 2006