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@article{2368736,
author = {Bychkova, Solomiia and Bychkov, Mykola and Dordevic, Dani and Vítězová, Monika and Rittmann, Simon K.andM. R. and Kushkevych, Ivan},
article_number = {3},
doi = {http://dx.doi.org/10.3390/ijms25031657},
keywords = {molecular mechanisms; colon cancer; ATPase; autophagy; hepatocytes; liver; NAADP; biomarkers; bafilomycin A1; Ca2+ store},
language = {eng},
issn = {1661-6596},
journal = {International Journal of Molecular Sciences},
title = {Bafilomycin A1 Molecular Effect on ATPase Activity of Subcellular Fraction of Human Colorectal Cancer and Rat Liver},
url = {https://www.mdpi.com/1422-0067/25/3/1657},
volume = {25},
year = {2024}
}
TY - JOUR
ID - 2368736
AU - Bychkova, Solomiia - Bychkov, Mykola - Dordevic, Dani - Vítězová, Monika - Rittmann, Simon K.-M. R. - Kushkevych, Ivan
PY - 2024
TI - Bafilomycin A1 Molecular Effect on ATPase Activity of Subcellular Fraction of Human Colorectal Cancer and Rat Liver
JF - International Journal of Molecular Sciences
VL - 25
IS - 3
SP - 1-18
EP - 1-18
PB - MDPI
SN - 16616596
KW - molecular mechanisms
KW - colon cancer
KW - ATPase
KW - autophagy
KW - hepatocytes
KW - liver
KW - NAADP
KW - biomarkers
KW - bafilomycin A1
KW - Ca2+ store
UR - https://www.mdpi.com/1422-0067/25/3/1657
N2 - 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.
ER -
BYCHKOVA, Solomiia, Mykola BYCHKOV, Dani DORDEVIC, Monika VÍTĚZOVÁ, Simon K.-M. R. RITTMANN and Ivan KUSHKEVYCH. Bafilomycin A1 Molecular Effect on ATPase Activity of Subcellular Fraction of Human Colorectal Cancer and Rat Liver. \textit{International Journal of Molecular Sciences}. MDPI, 2024, vol.~25, No~3, p.~1-18. ISSN~1661-6596. Available from: https://dx.doi.org/10.3390/ijms25031657.
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