Identification of the protein disulfide isomerase family member PDIp in experimental Parkinson's disease and Lewy body pathology
| Autor: | Kelly J. Conn, Patricia B. Eisenhauer, M. David Ullman, John M. Wells, Richard E. Fine, Wenwu Gao, Ann C. McKee, Michael S. Lan |
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| Rok vydání: | 2004 |
| Předmět: |
Male
medicine.medical_specialty 1-Methyl-4-phenylpyridinium Parkinson's disease Time Factors Dopamine Lactacystin Blotting Western Substantia nigra Tretinoin Biology chemistry.chemical_compound Neuroblastoma Parkinsonian Disorders Internal medicine Cell Line Tumor medicine Animals Humans RNA Messenger Protein disulfide-isomerase Molecular Biology Aged Aged 80 and over Analysis of Variance Lewy body Reverse Transcriptase Polymerase Chain Reaction General Neuroscience MPTP Neurodegeneration Nuclear Proteins Cell Differentiation Middle Aged medicine.disease Blotting Northern Molecular biology Immunohistochemistry Acetylcysteine Rats Endocrinology chemistry Proteasome Gene Expression Regulation Postmortem Changes Female Lewy Bodies Neurology (clinical) Developmental Biology |
| Zdroj: | Brain research. 1022(1-2) |
| ISSN: | 0006-8993 |
| Popis: | Parkinson's disease (PD) is a slowly progressing neurodegenerative disorder with no clear etiology. Pathological hallmarks of the disease include the loss of dopaminergic neurons from the substantia nigra (SN) and the presence of Lewy bodies (LBs) (alpha-synuclein and ubiquitin-positive, eosinophilic, cytoplasmic inclusions) in many of the surviving neurons. Experimental modeling of PD neurodegeneration using the neurotoxins 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenyl-pyridinium (MPP(+)) has identified changes in gene expression of different endoplasmic reticulum (ER) stress proteins associated with MPTP- and PD-related neurodegeneration. We show that the protein disulfide isomerase (PDI) family member pancreatic protein disulfide isomerase (PDIp), previously considered exclusively expressed in pancreatic tissue, is uniquely upregulated among PDI family members within 24 h following exposure of retinoic acid (RA)-differentiated SH-SY5Y human neuroblastoma cells to either 1 mM MPP(+) or 10 microM of the highly specific proteasome inhibitor lactacystin. RT-PCR confirms PDIp expression in brain of post-mortem human PD subjects and immunohistochemical studies demonstrate PDIp immunoreactivity in LBs. Collectively, these findings suggest that increased PDIp expression in dopaminergic (DA) neurons might contribute to LB formation and neurodegeneration, and that this increased PDIp expression may be the result of proteasome impairment. |
| Databáze: | OpenAIRE |
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