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
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- 作者：Michał Grabowski ; Bogdan Banecki ; Leszek Kadziński…
- 关键词：5 ; 10 ; methylenetetrahydrofolate reductase ; Escherichia coli MetF protein ; Human MTHFR gene ; Homocysteine ; Heat shock proteins
- 刊名：Metabolic Brain Disease
- 出版年：2016
- 出版时间：October 2016
- 年：2016
- 卷：31
- 期：5
- 页码：1041-1045
- 全文大小：498 KB
- 刊物类别：Biomedical and Life Sciences
- 刊物主题：Biomedicine
Neurosciences
Neurology
Biochemistry
Oncology - 出版者：Springer Netherlands
- ISSN：1573-7365
- 卷排序：31
文摘
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.