Participation of the transcription factor CREB1 in the regulation of the Mdh2 gene encoding malate dehydrogenase in the liver of rats with alloxan diabetes

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The aim of the study was to study the role of transcription factor CREB1 in regulating the expression of the gene encoding the mitochondrial form of malate dehydrogenase (MDH, EC 1.1.1.37) in the liver of rats with experimental diabetes. An increase in the rate of work of NAD-dependent malate dehydrogenase in rat liver cells during the development of experimental diabetes was shown, associated with the activation of the Mdh1 and Mdh2 genes encoding this enzyme. The analysis of the promoters of these genes showed that only in the Mdh2 gene there is a specific binding site with the transcription factor CREB1. It was found that in the liver of rats with pathology, there is an increase in the rate of expression of the gene encoding this transcription factor, which correlates with the expression of the Mdh2 gene. Thus, the data obtained by us confirm the possibility of positive regulation of the rate of the Mdh2 gene by the transcription factor CREB1.

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作者简介

A. Eprintsev

Voronezh State University

编辑信件的主要联系方式.
Email: bc366@bio.vsu.ru
俄罗斯联邦, Universitetskaya pl. 1, Voronezh, 394018

K. Romanenko

Voronezh State University

Email: bc366@bio.vsu.ru
俄罗斯联邦, Universitetskaya pl. 1, Voronezh, 394018

N. Selivanova

Voronezh State University

Email: bc366@bio.vsu.ru
俄罗斯联邦, Universitetskaya pl. 1, Voronezh, 394018

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2. Fig. 1. Concentration of glucose in the blood of healthy rats (Normal) and animals with alloxan diabetes (Diabetes), p < 0.007.

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3. Fig. 2. Relative level of Mdh1 and Mdh2 gene transcripts from the liver of rats of the control group (Normal) and animals with alloxan diabetes (Diabetes). When assessing the relative level of transcription of the studied genes in all groups of studied animals, statistically significant differences were revealed (* p < 0.009; ** p ≤ 0.001).

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4. Fig. 3. Alignment of the promoters of the rat Mdh1, Mdh2 and Sst1 genes (the somatotropin gene under the regulation of the transcription factor CREB1). The CRE site is highlighted with a rectangle.

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5. Fig. 4. Relative level of Creb1 gene transcripts from the liver of rats of the control group (Normal) and animals with alloxan diabetes (Diabetes). When assessing the relative level of Creb1 gene transcription in the experimental and control groups of animals, statistically significant differences were revealed (p < 0.001).

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6. Fig. 5. Structure of the Mdh1 (Gene ID: 24551) and Mdh2 (Gene ID: 81829) gene promoters in the rat genome. Inr – initiator and CG box (regulatory elements); The landing sites for the transcription factors ASCL1 (achaete-scute complex-like), FOXO1 and CREB1 are shown.

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7. Fig. 6. Electropherogram of PCR products after real-time PCR. M – DNA length markers 250–1000 bp. (Diaem, Russia), 1 and 5 – negative control, 2 and 6 – Mdh1 gene products, 3 and 7 – Mdh2 gene products, 4 and 8 – Eef1a1 gene products. Normal – a group of control rats, Diabetes – animals with alloxan diabetes.

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