Journal article
Protein kinase C-α regulation of gallbladder Na + transport becomes progressively more dysfunctional during gallstone formation
The Journal of laboratory and clinical medicine, v 146(4), pp 227-237
2005
PMID: 16194684
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Gallbladder Na
+ absorption and biliary Ca
2+ are both increased during gallstone formation and may promote cholesterol nucleation. Na
+/H
+exchange (NHE) is a major pathway for gallbladder Na
+ transport. Ca
2+-dependent second messengers, including protein kinase C (PKC), inhibit basal gallbladder Na
+ transport. Multiple PKC isoforms with species- and tissue-specific expression have been reported. In this study we sought to characterize Ca
2+-dependent PKC isoforms in gallbladder and to examine their roles in Na
+ transport during gallstone formation. Gallbladders were harvested from prairie dogs fed either nonlithogenic chow or 1.2% cholesterol-enriched diet for varying periods to induce various stages of gallstone formation. PKC was activated with the use of phorboldibutyrate, and we assessed gallbladder NHE regulation by measuring unidirectional Na
+ flux and dimethylamiloride-inhibitable
22Na
+ uptake. We measured gallbladder PKC activity with the use of histone III-S phosphorylation and used Gö 6976 to determine PKC-α contributions. Gallbladder PKC isoform messenger RNA and protein expression were examined with the use of Northern- and Western-blot analysis, respectively. Prairie dog and human gallbladder expresses PKC-α, βII, and δ isoforms. The PKC activation significantly decreased gallbladder J
Na
ms and reduced baseline
22Na
+ uptake by inhibiting NHE. PKC-α mediated roughly 42% of total PKC activity under basal conditions. PKC-α regulates basal gallbladder Na
+ transport by way of stimulation of NHE isoform NHE-2 and inhibition of isoform NHE-3. PKC-α blockade reversed PKC-induced inhibition of J
Na
ms and
22Na
+ uptake by about 45% in controls but was progressively less effective during gallstone formation. PKC-α contribution to total PKC activity is progressively reduced, whereas expression of PKC-α mRNA, and protein increases significantly during gallstone formation. We conclude that PKC-α regulation of gallbladder NHE becomes progressively more dysfunctional and may in part account for the increased Na
+ absorption observed during gallstone formation.
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Details
- Title
- Protein kinase C-α regulation of gallbladder Na + transport becomes progressively more dysfunctional during gallstone formation
- Creators
- Seth C. Narins - Drexel UniversityRamugounder Ramakrishnan - Drexel UniversityEun H. Park - Drexel UniversityPaul B. Bolno - Drexel UniversityDavid A. Haggerty - Drexel UniversityPeter R. Smith - University of Alabama at BirminghamWilliam C. Meyers - Drexel UniversityMohammad Z. Abedin - Drexel University
- Publication Details
- The Journal of laboratory and clinical medicine, v 146(4), pp 227-237
- Publisher
- Mosby, Inc
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Surgery
- Web of Science ID
- WOS:000232509900005
- Scopus ID
- 2-s2.0-25444437814
- Other Identifier
- 991019167426704721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Medical Laboratory Technology
- Medicine, Research & Experimental