title: 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.
abstract: The A222 V 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 A222 V substitution in MTHFR (caused by the C667T substitution in the MTHFR gene) can be ascribed to the A117 V substitution in MetF. Here, it is reported that a temperature-sensitive MetF117 (A117 V) 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 A222 V 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.
authors.affiliation: Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Kładki 24, 80-822, Gdańsk, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Grabowski
authors.affiliation: Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Kładki 24, 80-822, Gdańsk, Poland.
authors.forename: Bogdan
authors.initials: B
authors.lastname: Banecki
authors.affiliation: Intercollegiate Faculty of Biotechnology, University of Gdańsk and Medical University of Gdańsk, Kładki 24, 80-822, Gdańsk, Poland.
authors.forename: Leszek
authors.initials: L
authors.lastname: Kadziński
authors.affiliation: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jakóbkiewicz-Banecka
authors.affiliation: Laboratory of Molecular Biology (affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308, Gdańsk, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Gabig-Cimińska
authors.affiliation: Laboratory of Molecular Biology (affiliated with the University of Gdańsk), Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Wita Stwosza 59, 80-308, Gdańsk, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Węgrzyn
authors.affiliation: Department of Molecular Biology, University of Gdańsk, Wita Stwosza 59, 80-308, Gdańsk, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Węgrzyn
authors.affiliation: Department of Neurology, Medical University of Gdańsk, Dębinki 7, 80-211, Gdańsk, Poland. zytabm@gumed.edu.pl.
authors.forename: Zyta
authors.initials: Z
authors.lastname: Banecka-Majkutewicz
mesh_terms: D006360:Heat-Shock Proteins / Q000378:metabolism*; D006710:Homocysteine / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000378:metabolism*; D012307:Risk Factors; D020521:Stroke / Q000201:enzymology* / Q000517:prevention & control
chemical_list: D006360:Heat-Shock Proteins; D006710:Homocysteine; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2)
keywords: 5,10-methylenetetrahydrofolate reductase; Escherichia coli MetF protein; Heat shock proteins; Homocysteine; Human MTHFR gene