Tag Archives: ER stress
Biomarkers of apoptosis and endoplasmic reticulum stress in cardiomyocytes of rats under chronic ethanol consumption and germanium-nicotinic acid complex administration
I. V. Nizhenkovska1, O. V. Kuznetsova1,
V. P. Narokha1, D. O. Labudzynskyi2*
1Department of Medicinal Chemistry and Toxicology,
Bogomolets National Medical University, Kyiv, Ukraine;
2Department of Vitamins and Coenzyme Biochemistry,
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
*e-mail: labudzinskidmytro@gmail.com
Received: 11 November 2024; Revised: 03 February 2025;
Accepted: 21 February 2025; Available on-line: 03 March 2025
Chronic ethanol consumption is associated with a range of harmful effects on different systems of the body, including the heart. Coordination complexes of bioactive compounds based on non-toxic metals are attracting interest in biomedical research due to their potential therapeutic properties. The study aimed to evaluate the influence of the germanium-nicotinic acid complex (MIGU-1) on apoptosis and endoplasmic reticulum (ER) stress indicators in the myocardium of rats under chronic alcohol exposure. Female Wistar rats were divided into three groups of 6 animals each: intact animals; rats that received 20% ethanol as the sole source of liquid for 110 days; animals with chronic consumption of 20% ethanol, which from the 90th day until the end of the experiment were intraperitoneally administered MIGU-1 solution (10 mg/kg/day). Biomarkers related to apoptosis, ER stress autophagy were assessed by Western blot analysis. It was shown that chronic ethanol consumption significantly activated apoptotic pathways in rat myocardium tissue, evidenced by increased levels of cleaved caspase-3 and BAX proteins alongside Beclin-1 level elevation, indicating enhanced autophagy. A significant decrease in the content of the protein IRE1 and its phosphorylated form in myocardial with no changes in GRP78 protein level was detected. Treatment with MIGU-1 resulted in both ethanol-induced apoptosis reduction and ER stress attenuation in cardiomyocytes with the level of Beclin-1 and GRP78 proteins remaining unchanged. Our findings demonstrate that the MIGU-1 complex promotes cardiomyocyte survival by balancing apoptosis and unfolded protein response, thus preventing alcohol-related cardiac injury.
Serum glycomarkers of endoplasmic reticulum and lysosomal-endosomal system stress in human healthy aging and diseases
I. U. Pismenetskaya1, T. D. Butters2
1SI Dnepropetrovsk Medical Academy, Ukraine;
2CarboNet Consulting Ltd., Oxford, UK
e-mail: ip01589@gmail.com
To verify the idea that extracellular free oligosaccharides might be able to reflect the functional status of the endoplasmic reticulum (ER) and lysosomal-endosomal system, HPLC-profiles of serum-derived free oligosaccharides (FOS) in human healthy aging, acute myeloproliferative neoplasms, and cardiovascular pathologies were compared with intracellular glycans. After plasma deproteinization and FOS purification the oligosaccharides were labelled with anthranilic acid, separated into the neutral and charged with QAE Sephadex (Q25-120) chromatography and analysed using high-performance liquid chromatography (HPLC). The charged FOS were digested with a sialidase and compared with free oligosaccharides from transferrin for structural decoding. HPLC-profiles of serum-derived FOS revealed mild delay of the dolichol phosphate cycle in ER, moderate intensification of ER-associated degradation (ERAD) and degradation in endosomal-lysosomal system with aging; an inhibition of the dolichol phosphate cycle, intensification of ERAD and increasing of lysosomal exocytosis in acute myeloproliferative neoplasms; intensification of ERAD and glycocojugate degradation with endosomal-lysosomal system in cardiovascular diseases. As serum free oligosaccharides are able to reflect specifically perturbations in ER and endosomal-lysosomal system under wide range of stressors they can serve as extracellular markers of functionality of these organelles.