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; Simon K.-M. R. RITTMANN a Ivan KUSHKEVYCH

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: 4.900

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/24:00135445

Organizační jednotka

Přírodovědecká fakulta

EID Scopus

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 Novosadová 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