Inhibition of AMP‐ activated kinase (AMPK) mitigates zinc‐induced inhibition of urate secretion
Plasma urate level is primarily regulated by urinary excretion, and ~70% of urate excretion is due to tubular secretion. Birds, which only secrete urate, and humans, which secrete and reabsorb, maintain similar normal urate concentrations (~300 μM). Tubular secretion includes basolateral entry via Oat1/3‐like transport and apical membrane exit via Mrp4 transport, but regulating factors in the pathway remain uncertain. In other systems, cellular stress has been shown to affect transport properties by altering both stress protein levels and transporter expression or activity. We have shown that prolonged zinc‐induced cell stress inhibited active transepithelial urate secretion by chicken renal proximal tubule epithelial cell monolayers (cPTCs) with no change in Mrp4 expression, glucose transport, or transepithelial resistance. Acute exposure of cPTCs to zinc had no effect, nor was there an effect of zinc on urate uptake by isolated brush border membrane vesicles, suggesting involvement of a cellular stress adaptation. AMPK, which responds to cellular stress by shutting down non‐vital ATP‐utilizing processes, may be linked to this stress adaptation. Activation of AMPK by AICAR decreased urate secretion by cPTCs similar to the effect seen with zinc. The AMPK inhibitor, Compound C, prevented both AICAR and zinc inhibition of urate secretion. Supported by NSF..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2010 |
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| Erschienen: |
2010 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:24 |
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| Enthalten in: |
The FASEB Journal - 24(2010), Seite 1024.13-1024.13 |
| Beteiligte Personen: |
Bataille, Amy M. [VerfasserIn] |
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| BKL: |
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| Anmerkungen: |
© Federation of American Societies for Experimental Biology |
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| Umfang: |
1 |
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| doi: |
10.1096/fasebj.24.1_supplement.1024.13 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 520 | |a Plasma urate level is primarily regulated by urinary excretion, and ~70% of urate excretion is due to tubular secretion. Birds, which only secrete urate, and humans, which secrete and reabsorb, maintain similar normal urate concentrations (~300 μM). Tubular secretion includes basolateral entry via Oat1/3‐like transport and apical membrane exit via Mrp4 transport, but regulating factors in the pathway remain uncertain. In other systems, cellular stress has been shown to affect transport properties by altering both stress protein levels and transporter expression or activity. We have shown that prolonged zinc‐induced cell stress inhibited active transepithelial urate secretion by chicken renal proximal tubule epithelial cell monolayers (cPTCs) with no change in Mrp4 expression, glucose transport, or transepithelial resistance. Acute exposure of cPTCs to zinc had no effect, nor was there an effect of zinc on urate uptake by isolated brush border membrane vesicles, suggesting involvement of a cellular stress adaptation. AMPK, which responds to cellular stress by shutting down non‐vital ATP‐utilizing processes, may be linked to this stress adaptation. Activation of AMPK by AICAR decreased urate secretion by cPTCs similar to the effect seen with zinc. The AMPK inhibitor, Compound C, prevented both AICAR and zinc inhibition of urate secretion. Supported by NSF. | ||
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