Effects of Glutathione on the Expression of Atp-Sensitive Potassium Channels, Mitochondrial Pores, and on Oxidative Stress in the Heart of Old Rats

Abstract

The effects of a single injection of the reduced form of glutathione on the expression of the KCNJ8 and KCNJ11 genes encoding Kir6.1 and Kir6.2 subunits of ATP-sensitive potassium (KATP) channels and on Ca2+-induced nonspecific mitochondrial permeability transition pores (mPTP) opening in the heart of old rats were studied. Changes in biochemical parameters characterizing the intensity of oxidative processes in organelles at the action of glutathione were also studied. The expression levels of Kir6.1 і Kir6.2 subunits KATP channels were determined using reverse transcription and quantitative PCR. It was shown that after the administration of glutathione to old rats, the expression of KATP channel subunits significantly increased, namely for Kir6.1 9.3 times, for Kir6.2 2.6 times. The use of glutathione in older animals inhibited mPTP opening: reduced the amplitude of spontaneous and Ca2+-induced swelling of mitochondria. An important consequence of the action of glutathione during aging was a decrease in the rate of generation of superoxide (.О2-) and hydroxyl (.ОН) radicals, as well as the content of hydrogen peroxide respectively in 1.8, 2.5 and 3.2 times compared with these figures in older animals without treatment. Glutathione also reduced lipid peroxidation, particularly pools of diene conjugates (2.5-fold) and malonic dialdehyde (1.8-fold). Thus, glutathione significantly increases the expression of KCNJ8 and KCNJ11 genes encoding Kir6.1 and Kir6.2 subunits of KATP channels in the heart of rats, regulates MP, preventing its opening, and reduces oxidative stress, indicating its important role in myocardial protection.

Glutathione Upregulates the Expression of KATP Channels and Vasorelaxation Responses and Inhibits mPTP Opening and Oxidative Stress in the Heart Mitochondria of Old Rats

“…However, so far little attention has been paid to the study of the interaction of such powerful endogenous defense mechanisms as K ATP channels and glutathione. And if there is still information about improving the glutathione system functioning at activation of K ATP channels and about changing the activity of K ATP channels by glutathione, then, the mechanism of modulation of the expression of K ATP channels by GSH is shown for the first time by us [12][13][14]. The aim of this work was to study the possible influence of exogenous glutathione administration on regulating the expression of K ATP channels, mPTP opening in the heart, and vasorelaxation of isolated aortic rings upon activation of K ATP channels in old rats.…”