CARDIOMYOCYTE EXPRESSION OF METALLOTHIONEIN AND ZINC TRANSPORTER 1 IN RATS WITH ALDOSTERONISM: RESPONSE TO SPIRONOLACTONE OR AMLODIPINE COTREATMENT
| Autor: | Karl T. Weber, Robert A. Ahokas, Yao Sun, German Kamalov, N. Baburyan, Prajwal A. Deshmukh |
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| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Aldosterone Transporter General Medicine Pharmacology General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Endocrinology chemistry Internal medicine Toxicity medicine Collagenase Spironolactone Metallothionein Amlodipine Intracellular medicine.drug |
| Zdroj: | Journal of Investigative Medicine. 55:S255-S256 |
| ISSN: | 1081-5589 |
| DOI: | 10.1097/00042871-200701010-00568 |
| Popis: | Purpose In addition to the excessive accumulation of intracellular Ca2+ that appears in the myocardium with chronic aldosteronism, there is a rise in Zn and an increased expression of metallothionein (MT)-1, a Zn-binding protein, in cardiac tissue. Unlike other trace metals (eg, Cu, Fe, Co), whose excessive accumulation in a tissue is accompanied by cytotoxicity, tissue accumulation of Zn is devoid of such toxicity, which may relate to its inactivity mediated by intracellular binding and to transporters that expel it. Herein we hypothesized that Zn accumulation in cardiomyocytes is accompanied by increased expression of MT-1 and Znt-1, a Zn transporter (or exporter). Methods and Results Total mRNA was obtained from cardiomyocytes harvested by retrograde collagenase perfusion of the isolated rat heart. Quantitative real-time PCR was used to assess the mRNA expression of MT-1 and Znt-1 and a housekeeping gene tubulin. Their expression relative to control cells was calculated using the delta-delta Ct method. Cardiomyocytes were studied in four experimental groups; age-/gender-matched controls (C); aldosterone (0.75 μg/h) and 1% NaCl (A); 4 weeks A + spironolactone (S, 150 mg/kg/d by gavage); and A + amlodipine (CCB, 5 mg/kg/d by gavage). We found (p Conclusions In rats with aldosteronism, there is an increased expression of MT-1 and Znt-1 in cardiomyocytes that accompanies increased intracellular Zn and is likely a cytoprotective response to prevent Zn toxicity. Cotreatment with S attenuated these Zn-related responses, whereas amlodipine prevented the increased expression of MT-1 but not Znt-1. |
| Databáze: | OpenAIRE |
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