Methylglyoxal impairs glucose metabolism and leads to energy depletion in neuronal cells—protection by carbonyl scavengers

Garcia de Arriba, Susana, Stuchbury, Grant, Yarin, Jennifer, Burnell, Jim, Loske, Claudia, and Münch, Gerald (2007) Methylglyoxal impairs glucose metabolism and leads to energy depletion in neuronal cells—protection by carbonyl scavengers. Neurobiology of Aging, 28 (7). pp. 1044-1050.

[img] PDF
Restricted to Repository staff only

View at Publisher Website:


Advanced glycation end products (AGEs) are found in various intraneuronal protein deposits such as neurofibrillary tangles in Alzheimer's disease and Lewy bodies in Parkinson's disease. Among the many reactive carbonyl compounds and AGE precursors, methylglyoxal is most likely to contribute to intracellular AGE formation, since it is extremely reactive and constantly produced by degradation of triosephosphates. Furthermore, methylglyoxal levels increase under pathophysiological conditions, for example, when trisosephosphate levels are elevated, the expression or activity of glyoxalase I is decreased, as is the case when the concentration of reduced glutathione, the rate-determining co-factor of glyoxalase I, is low. However, the effects of methylglyoxal on mitochondrial function and energy levels have not been studied in detail. In this study, we show that methylglyoxal increases the formation of intracellular reactive oxygen species and lactate in SH-SY5Y neuroblastoma cells. Methylglyoxal also decreases mitochondrial membrane potential and intracellular ATP levels, suggesting that carbonyl stress-induced loss of mitochondrial integrity could contribute to the cytotoxicity of methylglyoxal. The methylglyoxal-induced effects such as ATP depletion and mitochondrial dysfunction can be prevented by pre-incubation of the cells with the carbonyl scavengers aminoguanidine and tenilsetam. In a clinical context, these compounds could not only offer a promising therapeutic strategy to reduce intracellular AGE-accumulation, but also to decrease the dicarbonyl-induced impairment of energy production in aging and neurodegeneration.

Item ID: 2520
Item Type: Article (Research - C1)
ISSN: 1558-1497
Keywords: methylglyoxal, Alzheimer's disease, mitochondria, reactive carbonyl compounds, mitochondrial membrane potential, aminoguanidine, tenilsetam, neurodegeneration, carbonyl stress, carbonyl scavengers
Date Deposited: 22 Jul 2009 06:54
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110999 Neurosciences not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 100%
Downloads: Total: 2
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page