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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2006-10-23
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pubmed:abstractText |
Parkinson disease (PD) is the second-most common age-related neurodegenerative disease and is characterized by the selective destruction of dopaminergic neurons. Increasing evidence indicates that oxidative stress plays a crucial role in the pathogenesis of idiopathic PD. Anti-oxidant agents including catalase, manganese porphyrin and pyruvate confer cytoprotection to different cell cultures when challenged with 6-hydroxydopamine (6-OHDA). Herein we used rat cerebellar granular cell cultures to ascertain the plausible cellular pathways involved in pyruvate-induced cytoprotection against 0.1 mM 6-OHDA. Pyruvate provided cytoprotection in a concentration-dependent manner (2-10 mM). Consistent with its well-established anti-oxidant capacity, pyruvate (10 mM) prevented 6-OHDA-induced lipid peroxidation by blocking the rise in intracellular peroxides and maintaining the intracellular reduced glutathione (GSH) levels. Further experiments revealed that pyruvate increased Akt, but not extracellular signal-regulated kinase phosphorylation. Moreover, phosphatidylinositol 3-kinase (PI3K) inhibitors attenuated pyruvate-induced cytoprotection indicating that PI3K-mediated Akt activation is necessary for pyruvate to induce cytoprotection. On the other hand, pyruvate also up-regulated glutathione peroxidase mRNA levels, but not those of the anti-oxidant enzymes superoxide dismutase-1 and -2, catalase or the anti-apoptotic oncogenes Bcl-2 or Bcl-xL. In summary, our results strongly suggest that pyruvate, besides the anti-oxidant properties related to its structure, exerts cytoprotective actions by activating different anti-apoptotic routes that include gene regulation and Akt pathway activation.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Peroxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidopamine,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/Pyruvic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0969-9961
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
24
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
296-307
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:16978869-Animals,
pubmed-meshheading:16978869-Animals, Newborn,
pubmed-meshheading:16978869-Antioxidants,
pubmed-meshheading:16978869-Apoptosis,
pubmed-meshheading:16978869-Cells, Cultured,
pubmed-meshheading:16978869-Cerebellar Cortex,
pubmed-meshheading:16978869-Cytoprotection,
pubmed-meshheading:16978869-Dose-Response Relationship, Drug,
pubmed-meshheading:16978869-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:16978869-Glutathione Peroxidase,
pubmed-meshheading:16978869-Lipid Peroxidation,
pubmed-meshheading:16978869-Nerve Degeneration,
pubmed-meshheading:16978869-Neurons,
pubmed-meshheading:16978869-Neuroprotective Agents,
pubmed-meshheading:16978869-Neurotoxins,
pubmed-meshheading:16978869-Oxidative Stress,
pubmed-meshheading:16978869-Oxidopamine,
pubmed-meshheading:16978869-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:16978869-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:16978869-Pyruvic Acid,
pubmed-meshheading:16978869-RNA, Messenger,
pubmed-meshheading:16978869-Rats,
pubmed-meshheading:16978869-Signal Transduction,
pubmed-meshheading:16978869-Up-Regulation
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pubmed:year |
2006
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pubmed:articleTitle |
Pyruvate protects cerebellar granular cells from 6-hydroxydopamine-induced cytotoxicity by activating the Akt signaling pathway and increasing glutathione peroxidase expression.
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pubmed:affiliation |
Departamento de Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha, and Servicio de Farmacia, Complejo Hospitalario Universitario de Albacete, Spain.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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