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The model homologue of the partially defective human 5,10-methylenetetrahydrofolate reductase, considered as a risk factor for stroke due to increased homocysteine level, can be protected and reactivated by heat shock proteins

Grabowski, Michał and Banecki, Bogdan and Kadziński, Leszek and Jakóbkiewicz-Banecka, Joanna and Gabig-Cimińska, Magdalena and Węgrzyn, Alicja and Węgrzyn, Grzegorz and Banecka-Majkutewicz, Zyta (2016) The model homologue of the partially defective human 5,10-methylenetetrahydrofolate reductase, considered as a risk factor for stroke due to increased homocysteine level, can be protected and reactivated by heat shock proteins. Metabolic Brain Disease, 31 (5). pp. 1041-1045. ISSN 0885-7490

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Official URL: https://link.springer.com/article/10.1007%2Fs11011...

Abstract

The A222V substitution in the human MTHFR gene product (5,10-methylenetetrahydrofolate reductase) is responsible for a decreased activity of this enzyme. This may cause an increased homocysteine level, considered as a risk factor for arteriosclerosis and stroke. The bacterial homologue of the human enzyme, MetF, has been found to be a useful model in genetic and biochemical studies. The similarity of Escherichia coli MetF and human MTHFR proteins is so high that particular mutations in the corresponding human gene can be reflected by the bacterial mutants. For example, the A222V substitution in MTHFR (caused by the C667T substitution in the MTHFR gene) can be ascribed to the A117V substitution in MetF. Here, it is reported that a temperature-sensitive MetF117 (A117V) protein can be partially protected from a thermal inactivation by the heat shock proteins from the Hsp70/100 systems. Moreover, activity of the thermally denatured enzyme can be partially restored by the same heat shock proteins. High temperature protein G (HtpG) had no effect on MetF117 activity in both experimental systems. The presented results indicate that functions of heat shock proteins may be required for maintenance of the MetF117 function. This may have implications for the mechanisms of arteriosclerosis and stroke, especially in the light of previous findings that the A222V MTHFR polymorphism may be a risk factor for stroke, as well as recently published results which demonstrated the increased levels of antibodies against heat shock proteins in stroke patients.

Item Type:Article
Subjects:Q Science > Q Science (General)
Q Science > QH Natural history
Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Divisions:Laboratory of Molecular Biology (in Gdansk)
ID Code:1223
Deposited By: Prof. Magdalena Gabig-Cimińska
Deposited On:14 Oct 2016 08:47
Last Modified:14 Oct 2016 08:47

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