{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T10:51:02Z","timestamp":1762080662491,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,12,20]],"date-time":"2022-12-20T00:00:00Z","timestamp":1671494400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Hyperuricemia is a risk factor for heart disease. Cardiomyocytes produce uric acid via xanthine oxidase. The enzymatic reaction leads to oxidative stress in uric-acid-producing cells. However, extracellular uric acid is the largest scavenger of reactive oxygen species, specifically to nitrosative stress, which can directly affect cells. Here, the effect of plasma-relevant concentrations of uric acid on adult rat ventricular cardiomyocytes is analyzed. A concentration- and time-dependent reduction of load-free cell shortening is found. This is accompanied by an increased protein expression of ornithine decarboxylase, the rate-limiting enzyme of the polyamine metabolism, suggesting a higher arginine turnover. Subsequently, the effect of uric acid was attenuated if other arginine consumers, such as nitric oxide synthase, are blocked or arginine is added. In the presence of uric acid, calcium transients are increased in cardiomyocytes irrespective of the reduced cell shortening, indicating calcium desensitization. Supplementation of extracellular calcium or stimulation of intracellular calcium release by \u03b2-adrenergic receptor stimulation attenuates the uric-acid-dependent effect. The effects of uric acid are attenuated in the presence of a protein kinase C inhibitor, suggesting that the PKC-dependent phosphorylation of troponin triggers the desensitizing effect. In conclusion, high levels of uric acid stress cardiomyocytes by accelerating the arginine metabolism via the upregulation of ornithine decarboxylase.<\/jats:p>","DOI":"10.3390\/biology12010004","type":"journal-article","created":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T02:31:33Z","timestamp":1671589893000},"page":"4","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Uric Acid Deteriorates Load-Free Cell Shortening of Cultured Adult Rat Ventricular Cardiomyocytes via Stimulation of Arginine Turnover"],"prefix":"10.3390","volume":"12","author":[{"given":"Martin","family":"Weber","sequence":"first","affiliation":[{"name":"Physiologisches Institut, Justus-Liebig-Universit\u00e4t, 35392 Gie\u00dfen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"Schreckenberg","sequence":"additional","affiliation":[{"name":"Physiologisches Institut, Justus-Liebig-Universit\u00e4t, 35392 Gie\u00dfen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6093-4919","authenticated-orcid":false,"given":"Klaus-Dieter","family":"Schl\u00fcter","sequence":"additional","affiliation":[{"name":"Physiologisches Institut, Justus-Liebig-Universit\u00e4t, 35392 Gie\u00dfen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1006\/jmcc.2002.1539","article-title":"Lethal effect of cytokine-induced nitric oxide and peroxynitrite on cultured rat cardiac myocytes","volume":"34","author":"Keira","year":"2002","journal-title":"J. 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