2-ethyl-6-methyl-3-hydroxypyridine carnitinate is a broad-spectrum adaptogen, that stimulates autophagy in liver tissue

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Дәйексөз келтіру

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Аннотация

Background: Under stress conditions, mitochondria become sources of excessive generation of reactive oxygen species (ROS), which can serve either as signaling molecules or damage cell structures. Antioxidants, reducing ROS generation, can serve as adaptogens to stress effects. It has been shown that a number of antioxidants are able to induce autophagy, which is able to activate the antioxidant-response element system. In this regard, the aim of the study was to investigate the anti-stress properties of a new antioxidant 2-ethyl-6-methyl-3-hydroxypyridine carnitinate (CP) and its ability to activate the synthesis of autophagy proteins Beclin-1, LC3.

Methods: Since the body’s resistance to stress factors primarily depends on energy metabolism, the effects of acute hypobaric hypoxia and CP on the LPO intensity in the lipid fraction of mice liver mitochondrial membranes were studied using the spectrofluorescence method. Autophagy proteins were determined by Western blotting using primary mice antibodies to Beclin-1 and LС3B proteins, as well as secondary antibodies labeled with horseradish peroxidase.

Results: Injection of 10–6 mol/kg CP to mice for 5 days prevented the growth of LPO intensity under conditions of acute hypobaric hypoxia (AHH). This drug increased life expectancy and increased survival of mice under conditions of various types of the hypoxia. The initiation of autophagy biomarker proteins (LC3B) by the drug was shown. At the same time, the content of Beclin-1 proteins tended to increase, which characterizes the onset of the autophagy process.

Conclusion: The new antioxidant CP can probably be used as an adaptogen to various types of hypoxia and an activator of autophagy.

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Рұқсат жабық

Авторлар туралы

Е. Mil

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

Email: elenamil2004@mail.ru
Moscow

I. Zhigacheva

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

Хат алмасуға жауапты Автор.
Email: elenamil2004@mail.ru
Ресей, Moscow

M. Korovin

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

Email: elenamil2004@mail.ru
Ресей, Moscow

V. Kuvyrkova

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

Email: elenamil2004@mail.ru
Ресей, Moscow

L. Matienko

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

Email: elenamil2004@mail.ru
Ресей, Moscow

A. Albantova

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

Email: albantovaaa@mail.ru
Ресей, Moscow

А. Goloshchapov

Emanuel Institute of Biochemical Physics, Russian Academy of Sciences

Email: elenamil2004@mail.ru
Ресей, Moscow

M. Rasulov

State Research Institute of Chemistry and Technology of Organoelement Compounds

Email: elenamil2004@mail.ru
Ресей, Mosсow

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2. Fig. 1. Structural formula of the antioxidant 2-ethyl-6-methyl-3-hydroxypyridine carnitinate (CP).

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3. Fig. 2. Effect of the putative autophagy initiator (CP preparation, 10–5 mol/kg and starvation) on the LC3B (a1–a4) and Beclin1 (b1, b2) protein content in mouse liver cells. The results of Western blot analysis (a1–a3, b1) and the corresponding densitograms (a4, b2) are shown. Electrophoresis was performed in 10% PAGE using the appropriate antibodies to detect protein bands; DAB staining. Designations: control — intact well-fed mice, starvation — mice after 2-day starvation, CP — mice after daily administration of CP for 3 days; MB — marker proteins. Repeated experiments on the introduction of CP to mice (control and starvation) were carried out at intervals of 1 month. The histograms show the average density values ​​of the LC3B and Biclin-1 protein bands. a1 — LC3B bands in all three variants; a2 — LC3B protein patterns appear upon introduction of CP; LC3A corresponds to a molecular weight of 16 kDa, and LC3B — 14 kDa. a3 — The density of LC3B bands upon introduction of CP is close to the density of bands upon 2-day starvation.

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4. Fig. 3. Effect of acute hypobaric hypoxia (AHB) against the background of CP (10–6 mol/kg for 5 days) on the fluorescence spectra of lipid peroxidation products in the membranes of mouse liver mitochondria. FI is the fluorescence intensity, conventional units per 1 mg of protein. Curves: 1 — AHB; 2 — CP + AHB (mice were subjected to 5-minute AHB 45 min after the end of CP); 3 — control.

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