J 2024

Bafilomycin A1 Molecular Effect on ATPase Activity of Subcellular Fraction of Human Colorectal Cancer and Rat Liver

BYCHKOVA, Solomiia, Mykola BYCHKOV, Dani DORDEVIC, Monika VÍTĚZOVÁ, Simon K.-M. R. RITTMANN et. al.

Základní údaje

Originální název

Bafilomycin A1 Molecular Effect on ATPase Activity of Subcellular Fraction of Human Colorectal Cancer and Rat Liver

Autoři

BYCHKOVA, Solomiia, Mykola BYCHKOV, Dani DORDEVIC, Monika VÍTĚZOVÁ (203 Česká republika, domácí), Simon K.-M. R. RITTMANN a Ivan KUSHKEVYCH (203 Česká republika, domácí)

Vydání

International Journal of Molecular Sciences, MDPI, 2024, 1661-6596

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10606 Microbiology

Stát vydavatele

Švýcarsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Impakt faktor

Impact factor: 5.600 v roce 2022

Organizační jednotka

Přírodovědecká fakulta

UT WoS

001161210700001

Klíčová slova anglicky

molecular mechanisms; colon cancer; ATPase; autophagy; hepatocytes; liver; NAADP; biomarkers; bafilomycin A1; Ca2+ store

Štítky

Příznaky

Mezinárodní význam, Recenzováno
Změněno: 23. 2. 2024 14:13, Mgr. Marie Šípková, DiS.

Anotace

V originále

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.

Návaznosti

MUNI/A/1280/2022, interní kód MU
Název: Podpora výzkumné činnosti studentů Mikrobiologie 3
Investor: Masarykova univerzita, Podpora výzkumné činnosti studentů Mikrobiologie 3
MUNI/A/1502/2023, interní kód MU
Název: Podpora výzkumné činnosti studentů Mikrobiologie 4
Investor: Masarykova univerzita, Podpora výzkumné činnosti studentů Mikrobiologie 4