| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Regular Articles |
From the Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
A better understanding of cellular mechanisms that occur in Parkinson’s disease and related Lewy body diseases is essential for development of new therapies. We previously found that 6-hydroxydopamine (6-OHDA) elicits sustained extracellular signal-regulated kinase (ERK) activation that contributes to neuronal cell death in vitro. As subcellular localization of activated kinases affect accessibility to downstream targets, we examined spatial patterns of ERK phosphorylation in 6-OHDA-treated cells and in human postmortem tissues representing the full spectrum of Lewy body diseases. All diseased human cases exhibited striking granular cytoplasmic aggregates of phospho-ERK (P-ERK) in the substantia nigra (involving 28 ± 2% of neurons), which were largely absent in control cases (0.3 ± 0.3%). Double-labeling studies and examination of preclinical cases suggested that these P-ERK alterations could occur relatively early in the disease process. Development of granular cytoplasmic P-ERK staining in 6-OHDA-treated cells was blocked by neuroprotective doses of catalase, supporting a role for oxidants in eliciting neurotoxic patterns of ERK activation. Evidence of nuclear translocation was not observed in degenerating neurons. Moreover, granular cytoplasmic P-ERK was associated with alterations in the distribution of downstream targets such as P-RSK1, but not of P-Elk-1, suggesting functional diversion of ERK-signaling pathways in Lewy body diseases.
This article has been cited by other articles:
 |
|
 |
|
  E. Nordstrom, G. Fisone, and K. Kristensson Opposing effects of ERK and p38-JNK MAP kinase pathways on formation of prions in GT1-1 cells FASEB J, February 1, 2009; 23(2): 613 - 622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Don Yi and J. W. Simpkins Protein Phosphatase 1, Protein Phosphatase 2A, and Calcineurin Play a Role in Estrogen-Mediated Neuroprotection Endocrinology, October 1, 2008; 149(10): 5235 - 5243. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Bonneh-Barkay, S. J. Bissel, G. Wang, K. N. Fish, G. C.B. Nicholl, S. W. Darko, R. Medina-Flores, M. Murphey-Corb, P. A. Rajakumar, J. Nyaundi, et al. YKL-40, a Marker of Simian Immunodeficiency Virus Encephalitis, Modulates the Biological Activity of Basic Fibroblast Growth Factor Am. J. Pathol., July 1, 2008; 173(1): 130 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Ma, K. A. Bower, G. Chen, X. Shi, Z.-J. Ke, and J. Luo Interaction between ERK and GSK3{beta} Mediates Basic Fibroblast Growth Factor-induced Apoptosis in SK-N-MC Neuroblastoma Cells J. Biol. Chem., April 4, 2008; 283(14): 9248 - 9256. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. D. Yi, Z. Y. Cai, D. F. Covey, and J. W. Simpkins Estrogen Receptor-Independent Neuroprotection via Protein Phosphatase Preservation and Attenuation of Persistent Extracellular Signal-Regulated Kinase 1/2 Activation J. Pharmacol. Exp. Ther., March 1, 2008; 324(3): 1188 - 1195. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mittal, D. Dubey, K. Yamakawa, and S. Ganesh Lafora disease proteins malin and laforin are recruited to aggresomes in response to proteasomal impairment Hum. Mol. Genet., April 1, 2007; 16(7): 753 - 762. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-h. Zhu, C. Horbinski, F. Guo, S. Watkins, Y. Uchiyama, and C. T. Chu Regulation of Autophagy by Extracellular Signal-Regulated Protein Kinases During 1-Methyl-4-Phenylpyridinium-Induced Cell Death Am. J. Pathol., January 1, 2007; 170(1): 75 - 86. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A.-L. Glotin, A. Calipel, J.-Y. Brossas, A.-M. Faussat, J. Treton, and F. Mascarelli Sustained versus Transient ERK1/2 Signaling Underlies the Anti- and Proapoptotic Effects of Oxidative Stress in Human RPE Cells. Invest. Ophthalmol. Vis. Sci., October 1, 2006; 47(10): 4614 - 4623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Klegeris, B. I. Giasson, H. Zhang, J. Maguire, S. Pelech, and P. L. McGeer Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells FASEB J, October 1, 2006; 20(12): 2000 - 2008. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Chalovich, J.-h. Zhu, J. Caltagarone, R. Bowser, and C. T. Chu Functional Repression of cAMP Response Element in 6-Hydroxydopamine-treated Neuronal Cells J. Biol. Chem., June 30, 2006; 281(26): 17870 - 17881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. St. P. McNaught, T. Jackson, R. JnoBaptiste, A. Kapustin, and C. W. Olanow Proteasomal dysfunction in sporadic Parkinson's disease Neurology, May 23, 2006; 66(10_suppl_4): S37 - S49. [Abstract] [Full Text]
|
|
|
|
 |
|
 K. D. Yi, J. Chung, P. Pang, and J. W. Simpkins Role of Protein Phosphatases in Estrogen-Mediated Neuroprotection J. Neurosci., August 3, 2005; 25(31): 7191 - 7198. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Callio, T. D. Oury, and C. T. Chu Manganese Superoxide Dismutase Protects against 6-Hydroxydopamine Injury in Mouse Brains J. Biol. Chem., May 6, 2005; 280(18): 18536 - 18542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. C. C. Cheung and R. S. Slack Emerging Role for ERK as a Key Regulator of Neuronal Apoptosis Sci. Signal., September 21, 2004; 2004(251): pe45 - pe45. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Chen, M. Rusnak, R. R. Luedtke, and A. Sidhu D1 Dopamine Receptor Mediates Dopamine-induced Cytotoxicity via the ERK Signal Cascade J. Biol. Chem., September 17, 2004; 279(38): 39317 - 39330. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Subramaniam, U. Zirrgiebel, O. von Bohlen und Halbach, J. Strelau, C. Laliberte, D. R. Kaplan, and K. Unsicker ERK activation promotes neuronal degeneration predominantly through plasma membrane damage and independently of caspase-3 J. Cell Biol., May 10, 2004; 165(3): 357 - 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Sawada, R. Kohno, T. Kihara, Y. Izumi, N. Sakka, M. Ibi, M. Nakanishi, T. Nakamizo, K. Yamakawa, H. Shibasaki, et al. Proteasome Mediates Dopaminergic Neuronal Degeneration, and Its Inhibition Causes {alpha}-Synuclein Inclusions J. Biol. Chem., March 12, 2004; 279(11): 10710 - 10719. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Boguslawski, P. W. McGlynn, K. A. Harvey, and A. T. Kovala SU1498, an Inhibitor of Vascular Endothelial Growth Factor Receptor 2, Causes Accumulation of Phosphorylated ERK Kinases and Inhibits Their Activity in Vivo and in Vitro J. Biol. Chem., February 13, 2004; 279(7): 5716 - 5724. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Mandell Phosphorylation State-Specific Antibodies: Applications in Investigative and Diagnostic Pathology Am. J. Pathol., November 1, 2003; 163(5): 1687 - 1698. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. S. Song, J.-K. Seong, K. C. Chung, W.-J. Lee, C.-H. Kim, K. N. Cho, C.-D. Kang, J. S. Koo, and J.-H. Yoon Induction of MUC8 Gene Expression by Interleukin-1{beta} Is Mediated by a Sequential ERK MAPK/RSK1/CREB Cascade Pathway in Human Airway Epithelial Cells J. Biol. Chem., September 12, 2003; 278(37): 34890 - 34896. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
