Linked Life Data

16375719

Source:http://linkedlifedata.com/resource/pubmed/id/16375719

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2005-12-26
pubmed:abstractText
The mechanism(s) of central nervous system complication associated with neurodegenerative disorders such as diabetes is unknown. Previous studies demonstrated that carbonyl stress induced by methylglyoxal (MG) mediates differential apoptosis of rat pheochromocytoma (PC12) cells in the naïve or differentiated transition states. Since chronic hyperglycemia is central to diabetic complications, and poorly differentiated cells are oxidatively more vulnerable, we currently investigated the effect of glycemic status on MG-induced apoptosis in naïve (nPC12) cells focusing on glutathione-to-glutathione disulfide (GSH/GSSG) redox signaling. nPC12 cells were exposed to 25 mM glucose acutely for 24h or chronically for 1 week. A role for glycemic fluctuation was tested in chronic high glucose-adapted cells subjected to acute reduction in glucose availability. Acute hyperglycemia potentiated MG-induced nPC12 apoptosis in accordance with cellular redox (GSH-to-Disulfide (GSSG plus protein-bound SSG)) imbalance. Chronic hyperglycemia exacerbated baseline and MG-induced apoptosis that corresponded to exaggerated loss of cytosolic and mitochondrial redox balance, impaired glucose 6-phosphate dehydrogenase (G6PD) activity, and enhanced basal expression of apoptosis protease activator factor-1 (Apaf-1). Reduced glucose availability in hyperglycemia-adapted nPC12 cells induced by acute lowering of glucose or by dehydroepiandrosterone (DHEA, G6PD inhibitor) further enhanced MG-induced apoptosis in association with greater cytosolic and mitochondrial redox and G6PD impairment and elevated basal Apaf-1 expression. These findings demonstrate that chronic hyperglycemia or acute glucose reduction from the chronic hyperglycemic state potentiates carbonyl stress, which collectively contribute to oxidative susceptibility of poorly differentiated cells such as that which occurs in brain neurons of neurodegenerative disorders like diabetes and Alzheimer's disease.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1567-2026
pubmed:author
pubmed:issnType
Print
pubmed:volume
2
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
375-86
pubmed:dateRevised
2011-9-22
pubmed:meshHeading
pubmed-meshheading:16375719-Animals, pubmed-meshheading:16375719-Apoptosis, pubmed-meshheading:16375719-Apoptotic Protease-Activating Factor 1, pubmed-meshheading:16375719-Brain, pubmed-meshheading:16375719-Cell Respiration, pubmed-meshheading:16375719-Dehydroepiandrosterone, pubmed-meshheading:16375719-Diabetes Complications, pubmed-meshheading:16375719-Enzyme Inhibitors, pubmed-meshheading:16375719-Glucose, pubmed-meshheading:16375719-Glucosephosphate Dehydrogenase, pubmed-meshheading:16375719-Glutathione, pubmed-meshheading:16375719-Glutathione Disulfide, pubmed-meshheading:16375719-Hyperglycemia, pubmed-meshheading:16375719-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:16375719-Neurodegenerative Diseases, pubmed-meshheading:16375719-Neurons, pubmed-meshheading:16375719-Oxidation-Reduction, pubmed-meshheading:16375719-Oxidative Stress, pubmed-meshheading:16375719-PC12 Cells, pubmed-meshheading:16375719-Protein Carbonylation, pubmed-meshheading:16375719-Proteins, pubmed-meshheading:16375719-Rats
pubmed:year
2005
pubmed:articleTitle
Hyperglycemia potentiates carbonyl stress-induced apoptosis in naïve PC-12 cells: relationship to cellular redox and activator protease factor-1 expression.
pubmed:affiliation
Department of Molecular and Cellular Physiology, LSU Health Sciences Center, 1501 Kings Highway, Shreveport, LA 71130-3932, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural