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ORIGINAL RESEARCH article
Front. Vet. Sci.
Sec. Animal Nutrition and Metabolism
Volume 11 - 2024 |
doi: 10.3389/fvets.2024.1480122
This article is part of the Research Topic The Role of Calcium Channels in Human Health and Disease Volume III View all articles
The impact of 3-sulfo-taurolithocholic acid on ATPase activity in patients' colorectal cancer and normal colon tissues, and its hepatic effects in rodents
Provisionally accepted- 1 Ivan Franko National University of Lviv, Lviv, Ukraine
- 2 Danylo Halytsky Lviv National Medical University, Lviv, Ukraine
- 3 University of Veterinary and Pharmaceutical Sciences Brno, Brno, South Moravia, Czechia
- 4 University of Vienna, Vienna, Austria
- 5 Masaryk University, Brno, South Moravia, Czechia
Colorectal cancer is influenced by genetic mutations, lifestyle factors, and diet, particularly high fat intake, which raises bile acid levels in the intestinal lumen. This study hypothesized that bile acids contribute to tumorigenesis by disrupting ion transport and ATPase activity in the intestinal mucosa.The effects of 3-sulfo-taurolithocholic acid (TLC-S) on ATPase activity were investigated in colorectal cancer samples from 10 patients, using adjacent healthy tissue as controls, and in rodent liver function. ATPase activity was measured spectrophotometrically by determining inorganic phosphorus (P i ) in postmitochondrial fractions. Ca 2+ dynamics were assessed in isolated mouse hepatocytes with fluorescence imaging, and rat liver mitochondria were studied using polarographic methods to evaluate respiration and oxidative phosphorylation. TLC-S increased Na + /K + ATPase activity by 1.5 times in colorectal cancer samples compared to controls (P ≤ 0.05). In healthy mucosa, TLC-S decreased Mg 2+ ATPase activity by 3.6 times (P ≤ 0.05), while Mg 2+ ATPase activity in cancer tissue remained unchanged. TLC-S had no significant effect on Ca 2+ ATPase activity in healthy colon mucosa but showed a trend towards decreased activity in cancer tissue. In rat liver, TLC-S decreased Ca 2+ ATPase and Na + /K + ATPase activities while increasing basal Mg 2+ 1 ATPase activity (P ≤ 0.05). Additionally, TLC-S induced cytosolic Ca 2+ signals in mouse hepatocytes, partially attenuated by NED-19, an NAADP antagonist (P ≤ 0.05). TLC-S also reduced the V3 respiration rate of isolated rat liver mitochondria during α-ketoglutarate oxidation.These findings suggest that TLC-S modulates ATPase activity differently in cancerous and healthy colon tissues, playing a role in colorectal cancer development. In rat liver, TLC-S affects mitochondrial activity and ATPase function, contributing to altered cytosolic calcium levels, providing insight into the mechanistic effects of bile acids on colorectal cancer and liver function.
Keywords: colorectal cancer, colon mucosae, Na+/K+ ATPase, Ca2+ ATPase, basal Mg2+ ATPase, Bile acid
Received: 14 Aug 2024; Accepted: 31 Oct 2024.
Copyright: © 2024 Bychkova, Bychkov, Dordevic, Rittmann, Monika and Kushkevych. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Simon K.-M. R. Rittmann, University of Vienna, Vienna, Austria
Ivan Kushkevych, Masaryk University, Brno, 601 77, South Moravia, Czechia
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