Glycation—a sweet tempter for neuronal death

Kikuchi, Seiji; Shinpo, Kazuyoshi; Takeuchi, Masayoshi; Yamagishi, Sho‐ichi; Makita, Zenji; Sasaki, Nobuyuki; Tashiro, Kunio

doi:10.1016/s0165-0173(02)00273-4

Cited by 155 publications

(96 citation statements)

References 113 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our research group has been studying different segments of the gastrointestinal tract for enteric neuropathies due to DM: Buttow et al (8) found a neuronal loss of 29.9% in the duodenum after 60 days of diabetes; in the ileum, Zanoni et al (40) observed a neuronal reduction of approximately 25% after 4 months of diabetes; finally, Zanoni et al (38) found a neuronal loss of 34.6% in the cecum of rats submitted to 8 months of DM. There are several mechanisms that causes myenteric density reduction in function of diabetes and hyperglycemia, we can list: 1) the elevated production of sorbitol, since it causes cell death by increasing the osmolarity in the neuron leading to edema and to a reduction in the transmission of nerve impulses (9,10) ; 2) the auto-oxidative glycosylation (25) and non-enzymatic glycation (23) , that increase oxidative stress; 3) lipid peroxidation, which destroys the cell membranes (32) , and finally, 4) the metabolic process described above, when coupled with frequent inflammatory responses, which help to generate reactive oxygen species (3,12) . The neuropathy, in diabetic condition, develops when the natural antioxidant systems cannot overcome the oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

Effects of L-glutamine supplementation on the myenteric neurons from the duodenum and cecum of diabetic rats

Zanoni

Tronchini

Moure

et al. 2011

Arq. Gastroenterol.

View full text Add to dashboard Cite

-Context -Peripheral neuropathy is one of the chronic complications of diabetes mellitus and is directly related to gastrointestinal consequences of the disease. Myenteric neurons are affected in some pathological conditions such as diabetic neuropathy.The imbalance between cellular antioxidants and free radicals, leading to an increase in oxidative stress, is considered one of the main factors responsible for neuronal damages in diabetes. Drugs that reduce the oxidative stress may play a significant role in the treatment of neurological complications of diabetes mellitus. Objective -To evaluate the effect of L-glutamine supplementation on the myenteric neurons from the cecum and duodenum of Wistar rats with streptozotocin-induced diabetes mellitus. Methods -The animals were divided in four groups (n = 5): non-treated normoglycemics, normoglycemics treated with L-glutamine, non-treated diabetics and diabetics treated with L-glutamine from the 4th day of diabetes induction on. The amino acid L-glutamine was added to their diet at 1%. Giemsa's technique was employed to stain the myenteric neurons. We determined the cell body area of 500 neurons in each group studied. The quantitative analysis was performed by sampling in an area of 16.6 mm 2 in the cecum and 3.6 mm 2 in the duodenum of each animal. Results -After the supplementation with L-glutamine in the duodenum, we observed a preservation of neuronal density in groups normoglycemic and diabetic (P<0.05). We also observed a preservation of the cell bodies area in diabetic animals (group treated with L-glutamine) (P<0.05). In the cecum, that preservation was not evident. Conclusion -Supplementation with L-glutamine (1%) promoted a neuroprotective effect on the myenteric neurons from the duodenum of rats, both in terms of natural aging and of diabetes mellitus.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of L-glutamine supplementation on the myenteric neurons from the duodenum and cecum of diabetic rats

Zanoni

Tronchini

Moure

et al. 2011

Arq. Gastroenterol.

View full text Add to dashboard Cite

show abstract

“…The accumulation of glycation adducts results in deleterious consequences including oxidative stress, DNA damage, and apoptosis. Also, methylglyoxal is toxic to neurons and may contribute to the neurological symptoms observed in patients (36). Under oxidative stress conditions glyoxalases cannot efficiently detoxify methylglyoxal, which may underlie the associated neurodegeneration (37).…”

Section: Consequences Of Tpi Impairment At the System Levelmentioning

confidence: 99%

Triosephosphate isomerase deficiency: Facts and doubts

Orosz

Oláh

Ovádi

2006

TBMB

108

111

View full text Add to dashboard Cite

SummaryMany glycolytic enzymopathies have been described that manifest clinically as chronic hemolytic anemia. One of these, triosephosphate isomerase (TPI) deficiency, is unique among the glycolytic enzyme defects since it is associated with progressive neurological dysfunction and frequently with childhood death. The physiological function of TPI is to adjust the rapid equilibrium between dihydroxyacetone phosphate and glyceraldehyde-3-phosphate produced by aldolase in glycolysis, which is interconnected to the pentose phosphate pathway and to lipid metabolism via triosephosphates. The TPI gene is well characterized; structure and function studies suggest that instability of the isomerase due to different mutations of the enzyme may underlie the observed reduced catalytic activity. Patients with various inherited mutations have been identified. The most abundant mutation is a Glu104Asp missense mutation that is found in homozygotes and compound heterozygotes. Two germ-line identical Hungarian compound heterozygote brothers with distinct phenotypes question the exclusive role of the inherited mutations in the etiology of neurodegeneration. This paper: (i) reviews our present understanding of TPI mutation-induced structural alterations and their pathological consequences, (ii) summarizes the consequences of TPI impairment in the Hungarian case at local and system levels, and (iii) raises critical questions regarding the exclusive role of TPI mutations in the development of this human disease.

show abstract

“…Despite that CML has been detected in AD lesions by immunohistochemical analyses (reviewed in Ref. 10), no chemical evidence have been reported for this product in AD samples or models. Polyunsaturated fatty acids (PUFA) are other third-party molecules.…”

mentioning

confidence: 99%

Proteins in Human Brain Cortex Are Modified by Oxidation, Glycoxidation, and Lipoxidation

Pamplona

Dalfó

Ayala

et al. 2005

Journal of Biological Chemistry

258

242

View full text Add to dashboard Cite

Diverse oxidative pathways, such as direct oxidation of amino acids, glycoxidation, and lipoxidation could contribute to Alzheimer disease pathogenesis. A global survey for the amount of structurally characterized probes for these reactions is lacking and could overcome the lack of specificity derived from measurement of 2,4-dinitrophenylhydrazine reactive carbonyls. Consequently we analyzed (i) the presence and concentrations of glutamic and aminoadipic semialdehydes, N ⑀ -(carboxymethyl)-lysine, N ⑀ -(carboxyethyl)-lysine, and N ⑀ -(malondialdehyde)-lysine by means of gas chromatography/mass spectrometry, (ii) the biological response through expression of the receptor for advanced glycation end products, (iii) the fatty acid composition in brain samples from Alzheimer disease patients and agematched controls, and (iv) the targets of N ⑀ -(malondialdehyde)-lysine formation in brain cortex by proteomic techniques. Alzheimer disease was associated with significant, although heterogeneous, increases in the concentrations of all evaluated markers. Alzheimer disease samples presented increases in expression of the receptor for advanced glycation end products with high molecular heterogeneity. Samples from Alzheimer disease patients also showed content of docosahexaenoic acid, which increased lipid peroxidizability. In accordance, N ⑀ -(malondialdehyde)-lysine formation targeted important proteins for both glial and neuronal homeostasis such as neurofilament L, ␣-tubulin, glial fibrillary acidic protein, ubiquinol-cytochrome c reductase complex protein I, and the ␤ chain of ATP synthase. These data support an important role for lipid peroxidationderived protein modifications in Alzheimer disease pathogenesis.

show abstract

Glycation—a sweet tempter for neuronal death

Cited by 155 publications

References 113 publications

Effects of L-glutamine supplementation on the myenteric neurons from the duodenum and cecum of diabetic rats

Effects of L-glutamine supplementation on the myenteric neurons from the duodenum and cecum of diabetic rats

Triosephosphate isomerase deficiency: Facts and doubts

Proteins in Human Brain Cortex Are Modified by Oxidation, Glycoxidation, and Lipoxidation

Contact Info

Product

Resources

About