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1

Plasma homocysteine level and the course of ischemic stroke

100%

Pniewski J., Chodakowska-Zebrowska M., Wozniak R., Stepien K., Stafiej A.

Acta Neurobiologiae Experimentalis

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2003

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vol. 63

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issue 2

127-130

EN

Increased level of homocysteine (Hcy) in blood seems to influence negatively the course of ischemic stroke (IS), the possible mechanism of this action could be acceleration of oxidative stress. The aim of this study is to assess the influence of Hcy level in patients with IS on the prognosis 3 moths after the stroke onset. 75 patients aged 68.27 12.62 years, with the diagnosis of first ever IS were examined. Patients with the symptoms corresponding with TACS at the beginning of stroke and with diminished level of consciousness were not included. The level of Hcy over 15 mol/l was assessed as mild hiperhomocysteinemia (MHcy). 74 (98.7%) patients were assessed 3 months after IS onset in the Rankin scale. Recovery was assessed, according to Rankin Scale: good recovery (GR) 0-2, bad recovery (BR) 3-5 and death. MHcy was seen in 9 (14.5%) with GR and in 8 (66.7%) with BR (P=0,0005). MHcy increases the risk of BR 11.78 times (95%CI 2.93-47.42).

2

Excitotoxic neuronal injury in chronic homocysteine neurotoxicity studied in vitro: The role of NMDA and group I metabotropic glutamate receptors

88%

Zieminska E., Lazarewicz J. W.

Acta Neurobiologiae Experimentalis

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2006

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vol. 66

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issue 4

301-309

EN

Elevated homocysteine is a risk factor in cardiovascular diseases and neurodegeneration. Among the putative mechanisms of homocysteine-evoked neurotoxicity, disturbances in methylation processes and NMDA receptor-mediated excitotoxicity have been suggested. Our previous studies demonstrated that group I metabotropic glutamate receptors along with NMDA receptors participate in acute homocysteine-induced neuronal damage. In this study, using propidium iodide staining, we tested whether the same mechanism may mediate chronic homocysteine neurotoxicity. Our results confirmed that the application of D,L-homocysteine in micromolar concentrations for 3 days induces neurodegeneration in primary cultures of cerebellar granule neurons. Uncompetitive NMDA receptor antagonist MK-801, and mGlu1 or mGlu5 receptor antagonists (LY367385 and MPEP, respectively), given alone provided very limited neuroprotection. However, simultaneous application of the NMDA receptor antagonists MK-801, memantine or amantadine and MPEP almost completely prevented chronic homocysteine neurotoxicity. These findings suggest a novel therapeutic strategy to combat neurodegeneration induced by hyperhomocysteinemia comprising a combination of antagonists of group I metabotropic glutamate receptors and NMDA receptors.

3

Polymorphism of methylenetetrahydrofolate reductase gene (Mthfr) and occurrence of the hyperhomocyteinemia-related diseases

88%

Pawlak A. L., Strauss E., Pawlak A. L.

Postępy Higieny i Medycyny Doświadczalnej

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2001

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vol. 55

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issue 2

233-256

EN

Methylenetetrahydrofolate reductase (MTHFR), is a cytosolic enzyme, the product of which is N5-metyltetrahydrofolate, the main form of folates in tissues and the carbon donor for methylation of homocysteine to methionine. In MTHFR gene a series of the pathogenic mutations is known which lead to loss of enzymatic activity as well as the two polymorphic alleles (MTHFR 677T and 1298C) with products displaying the lowered enzyme activity resulting in hyperhomocysteinaemia. These polymorphic alleles of MTHFR represent the main genetic factor contributing to hyperhomocysteinaemia. The better known allele MTHFR 677T is found in different populations with frequency between ca. 0,1 and 0,36. In persons inheriting the variant alleles of MTHFR the increase in the level of homocysteine is noted resulting in the increased susceptibility to vascular diseases and the neural tube defects in the progeny. The procedure recommended for the prevention of effects of deficiency of MTHFR activity consists of the supplementation of the diet with 0,4 mg of folic acid daily.

4

C677T polymorphism of the methylenetetrahydrofolate reductase gene and the risk of ischemic stroke in Polish subjects

88%

Goracy I., Cyrylowski L., Kaczmarczyk M., Fabian A., Koziarska D., Goracy J., Ciechanowicz A.

Journal of Applied Genetics

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2009

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vol. 50

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issue 1

63-67

EN

Hyperhomocysteinemia is reported to be an independent risk factor for the development of ischemic stroke. Several studies on genetic variants of methylenetetrahydrofolate reductase (MTHFR, which plays a crucial role in regulation of plasma homocysteine concentration) reported an association between C677T gene polymorphism and stroke in some Asian populations. No study but one detected this association in Caucasians. The purpose of the present case-control study was to find a relationship between MTHFR genotypes and stroke in a Polish population. MTHFR genotypes were determined by PCR in 152 patients with ischemic stroke from northwestern Poland and in 135 consecutive newborns from the same population. The TT genotype and the T allele were significantly more frequent in patients than in the control group (11.8% vs. 4.4%, and 34.5% vs. 21.5%, P < 0.01). When males and females were analyzed separately, the differences were statistically significant in both genders. It is concluded that presence of the T allele is a risk factor for ischemic stroke in Polish subjects.

5

Oxidative DNA damage and level of thiols as related to polymorphisms of MTHFR, MTR, MTHFD1 in Alzheimer's and Parkinson's diseases

88%

Dorszewska J., Florczak J., Rozycka A., Kempisty B., Jaroszewska-Kolecka J., Chojnacka K., Trzeciak W. H., Kozubski W.

Acta Neurobiologiae Experimentalis

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2007

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vol. 67

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issue 2

113-129

EN

Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are accompanied by increased levels of 8-oxo-2'-deoxyguanosine (8-oxo2dG) and alterations in levels of homocysteine (Hcy), methionine (Met), and cysteine (Cys). Hcy may undergo remethylation due to involvement of MTHFR, MTR and MTHFD1 proteins. Present studies are aimed at determination of 8-oxo2dG, Hcy, Met, and Cys in AD and PD patients as well as in control groups, using HPLC/EC/UV, as well as estimation, by restriction analysis, frequency of following gene polymorphisms: MTHFR (C677T, A1298C, G1793A), MTHFD1 (G1958A), and MTR (A2756G). In AD there were significant differences of the levels of only Cys (GG, MTHFR, G1793A) and Met/Hcy (AA, MTHFD1, G1958A) whereas in PD there were more significant differences of the levels of thiols: Hcy [MTHFR: CT (C677T) and GG (G1793A); MTR, AG (A2756G)], Met [MTR, AA (A2756G)], Cys [MTR, AG (A2756G)], and Met/Hcy [MTHFR: CC, CT (C677T) and AA (A1298C), and GG (G1793A); MTHFD1 AA(G1958A); MTR AA(A2756G)]. Significant differences in the levels of Cys/Hcy, MTHFD1 GA (G1958) were varied between AD and PD groups. The results indicate that of the enzymes studied only polymorphisms of folate-dependent enzyme MTHFD1 have pointed to significant differences in intensity of turnover of circulating thiols between AD and PD patients.

6

Nicotinamide and 1-methylnicotinamide reduce homocysteine neurotoxicity in primary cultures of rat cerebellar granule cells

75%

Slomka M., Zieminska E., Lazarewicz J. W.

Acta Neurobiologiae Experimentalis

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2008

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vol. 68

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issue 1

1-9

EN

Nicotinamide is an important cofactor in many metabolic pathways and a known neuroprotective substance, while its methylated product, 1-methylnicotinamide, is a suspected neurotoxin. Homocysteine is a risk factor in Alzheimer's disease and neurodegeneration, causing inhibition of methylation processes and inducing excitotoxicity. In this study, using primary cultures of rat cerebellar granule cells and propidium iodide staining, we investigated the neurotoxicity of nicotinamide and 1-methylnicotinamide, and their neuroprotective potential in acute and sub-acute homocysteine neurotoxicity. Our results demonstrated that nicotinamide and 1-methylnicotinamide applied for 24 h to cultures at concentrations of up to 25 mM had no effect on neuronal viability. Moreover, nicotinamide at concentrations of 5?20 mM and 1-methylnicotinamide at 1?10 mM applied to cells 24 h before, and for 24 h after an acute 30 min application of 25 mM D,L homocysteine, reduced neuronal damage. 1-Methylnicotinamide at concentrations of 250 and 500 ?M showed neuroprotective activity during a sub-acute 24-h exposure to 2.5 mM D,L-homocysteine, while 5 and 25 mM nicotinamide also evoked neuroprotection. These findings do not support suggestions that 1-methylnicotinamide may act as an endogenous neurotoxic agent; rather, they indicate the neuroprotective ability of nicotinamide and 1-methylnicotinamide in homocysteine neurotoxicity. The exact mechanisms of this neuroprotection are unclear and require further investigation.

Refine search results

Plasma homocysteine level and the course of ischemic stroke

Excitotoxic neuronal injury in chronic homocysteine neurotoxicity studied in vitro: The role of NMDA and group I metabotropic glutamate receptors

Polymorphism of methylenetetrahydrofolate reductase gene (Mthfr) and occurrence of the hyperhomocyteinemia-related diseases

C677T polymorphism of the methylenetetrahydrofolate reductase gene and the risk of ischemic stroke in Polish subjects

Oxidative DNA damage and level of thiols as related to polymorphisms of MTHFR, MTR, MTHFD1 in Alzheimer's and Parkinson's diseases

Nicotinamide and 1-methylnicotinamide reduce homocysteine neurotoxicity in primary cultures of rat cerebellar granule cells