Bafilomycin A1 Molecular Effect on ATPase Activity of Subcellular Fraction of Human Colorectal Cancer and Rat Liver
- Autor(en)
- Solomiia Bychkova, Mykola Bychkov, Dani Dordevic, Monika Vítězová, Simon K-M R Rittmann, Ivan Kushkevych
- Abstrakt
Bafilomycin A1 inhibits V-type H+ ATPases on the molecular level, which acidifies endo-lysosomes. The main objective of the study was to assess the effect of bafilomycin A1 on Ca2+ content, NAADP-induced Ca2+ release, and ATPase activity in rat hepatocytes and human colon cancer samples. Chlortetracycline (CTC) was used for a quantitative measure of stored calcium in permeabilized rat hepatocytes. ATPase activity was determined by orthophosphate content released after ATP hydrolysis in subcellular post-mitochondrial fraction obtained from rat liver as well as from patients' samples of colon mucosa and colorectal cancer samples. In rat hepatocytes, bafilomycin A1 decreased stored Ca2+ and prevented the effect of NAADP on stored Ca2+. This effect was dependent on EGTA-Ca2+ buffers in the medium. Bafilomycin A1 significantly increased the activity of Ca2+ ATPases of endoplasmic reticulum (EPR), but not plasma membrane (PM) Ca2+ ATPases in rat liver. Bafilomycin A1 also prevented the effect of NAADP on these pumps. In addition, bafilomycin A1 reduced Na+/K+ ATPase activity and increased basal Mg2+ ATPase activity in the subcellular fraction of rat liver. Concomitant administration of bafilomycin A1 and NAADP enhanced these effects. Bafilomycin A1 increased the activity of the Ca2+ ATPase of EPR in the subcellular fraction of normal human colon mucosa and also in colon cancer tissue samples. In contrast, it decreased Ca2+ ATPase PM activity in samples of normal human colon mucosa and caused no changes in colon cancer. Bafilomycin A1 decreased Na+/K+ ATPase activity and increased basal Mg2+ ATPase activity in normal colon mucosa samples and in human colon cancer samples. It can be concluded that bafilomycin A1 targets NAADP-sensitive acidic Ca2+ stores, effectively modulates ATPase activity, and assumes the link between acidic stores and EPR. Bafilomycin A1 may be useful for cancer therapy.
- Organisation(en)
- Department für Funktionelle und Evolutionäre Ökologie
- Externe Organisation(en)
- Ivan Franko National University of Lviv, Danylo Halytsky Lviv National Medical University, Veterinární univerzita Brno , Masaryk University
- Journal
- International Journal of Molecular Sciences
- Band
- 25
- ISSN
- 1422-0067
- DOI
- https://doi.org/10.3390/ijms25031657
- Publikationsdatum
- 01-2024
- Peer-reviewed
- Ja
- ÖFOS 2012
- 106022 Mikrobiologie
- Schlagwörter
- ASJC Scopus Sachgebiete
- Molecular Biology, Spectroscopy, Catalysis, Inorganic Chemistry, Computer Science Applications, Physical and Theoretical Chemistry, Organic Chemistry
- Sustainable Development Goals
- SDG 3 – Gesundheit und Wohlergehen
- Link zum Portal
- https://ucris.univie.ac.at/portal/de/publications/bafilomycin-a1-molecular-effect-on-atpase-activity-of-subcellular-fraction-of-human-colorectal-cancer-and-rat-liver(21a1db69-c9e6-4380-860c-55761c7a901a).html