Adaptive downregulation of Cl- /HCO3 - exchange activity in rat hepatocytes under experimental obstructive cholestasis
In obstructive cholestasis, there is an integral adaptive response aimed to diminish the bile flow and minimize the injury of bile ducts caused by increased intraluminal pressure and harmful levels of bile salts and bilirrubin. Canalicular bicarbonate secretion, driven by the anion exchanger 2 (A...
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| Autores principales: | , , , , , , , , |
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| Formato: | article artículo publishedVersion |
| Lenguaje: | Inglés |
| Publicado: |
Public Library of Science (PLOS)
2021
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| Materias: | |
| Acceso en línea: | http://hdl.handle.net/2133/19973 http://hdl.handle.net/2133/19973 |
| Aporte de: |
| id |
I15-R121-2133-19973 |
|---|---|
| record_format |
dspace |
| institution |
Universidad Nacional de Rosario |
| institution_str |
I-15 |
| repository_str |
R-121 |
| collection |
Repositorio Hipermedial de la Universidad Nacional de Rosario (UNR) |
| language |
Inglés |
| orig_language_str_mv |
eng |
| topic |
Obstructive Cholestasis Chloride-Bicarbonate Antiporters Transporter Localization Transporter Expression |
| spellingShingle |
Obstructive Cholestasis Chloride-Bicarbonate Antiporters Transporter Localization Transporter Expression Miszczuk, Gisel Sabrina Banales, Jesus M. Zucchetti, Andrés E. Pisani, Gerardo Bruno Boaglio, Andrea C. Saez, Elena Medina, Juan F. Roma, Marcelo Gabriel Crocenzi, Fernando A. Adaptive downregulation of Cl- /HCO3 - exchange activity in rat hepatocytes under experimental obstructive cholestasis |
| topic_facet |
Obstructive Cholestasis Chloride-Bicarbonate Antiporters Transporter Localization Transporter Expression |
| description |
In obstructive cholestasis, there is an integral adaptive response aimed to diminish the bile
flow and minimize the injury of bile ducts caused by increased intraluminal pressure and
harmful levels of bile salts and bilirrubin. Canalicular bicarbonate secretion, driven by the
anion exchanger 2 (AE2), is an influential determinant of the canalicular bile salt-independent bile flow. In this work, we ascertained whether AE2 expression and/or activity is
reduced in hepatocytes from rats with common bile duct ligation (BDL), as part of the adaptive response to cholestasis. After 4 days of BDL, we found that neither AE2 mRNA expression (measured by quantitative real-time PCR) nor total levels of AE2 protein (assessed by
western blot) were modified in freshly isolated hepatocytes. However, BDL led to a decrease
in the expression of AE2 protein in plasma membrane fraction as compared with SHAM control. Additionally, AE2 activity (JOH-, mmol/L/min), measured in primary cultured hepatocytes
from BDL and SHAM rats, was decreased in the BDL group versus the control group (1.9 ±
0.3 vs. 3.1 ± 0.2, p<0.005). cAMP-stimulated AE2 activity, however, was not different
between SHAM and BDL groups (3.7 ± 0.3 vs. 3.5 ± 0.3), suggesting that cAMP stimulated
insertion into the canalicular membrane of AE2-containing intracellular vesicles, that had
remained abnormally internalized after BDL. In conclusion, our results point to the existence
of a novel adaptive mechanism in cholestasis aimed to reduce biliary pressure, in which
AE2 internalization in hepatocytes might result in decreased canalicular HCO3
-
output and
decreased bile flow. |
| format |
article artículo publishedVersion |
| author |
Miszczuk, Gisel Sabrina Banales, Jesus M. Zucchetti, Andrés E. Pisani, Gerardo Bruno Boaglio, Andrea C. Saez, Elena Medina, Juan F. Roma, Marcelo Gabriel Crocenzi, Fernando A. |
| author_facet |
Miszczuk, Gisel Sabrina Banales, Jesus M. Zucchetti, Andrés E. Pisani, Gerardo Bruno Boaglio, Andrea C. Saez, Elena Medina, Juan F. Roma, Marcelo Gabriel Crocenzi, Fernando A. |
| author_sort |
Miszczuk, Gisel Sabrina |
| title |
Adaptive downregulation of Cl- /HCO3 - exchange activity in rat hepatocytes under experimental obstructive cholestasis |
| title_short |
Adaptive downregulation of Cl- /HCO3 - exchange activity in rat hepatocytes under experimental obstructive cholestasis |
| title_full |
Adaptive downregulation of Cl- /HCO3 - exchange activity in rat hepatocytes under experimental obstructive cholestasis |
| title_fullStr |
Adaptive downregulation of Cl- /HCO3 - exchange activity in rat hepatocytes under experimental obstructive cholestasis |
| title_full_unstemmed |
Adaptive downregulation of Cl- /HCO3 - exchange activity in rat hepatocytes under experimental obstructive cholestasis |
| title_sort |
adaptive downregulation of cl- /hco3 - exchange activity in rat hepatocytes under experimental obstructive cholestasis |
| publisher |
Public Library of Science (PLOS) |
| publishDate |
2021 |
| url |
http://hdl.handle.net/2133/19973 http://hdl.handle.net/2133/19973 |
| work_keys_str_mv |
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