{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T16:18:31Z","timestamp":1777738711448,"version":"3.51.4"},"reference-count":46,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,8,18]],"date-time":"2011-08-18T00:00:00Z","timestamp":1313625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2011,8,18]],"date-time":"2011-08-18T00:00:00Z","timestamp":1313625600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Cellular Biochemistry"],"published-print":{"date-parts":[[2011,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Brown spider venom phospholipase\u2010D belongs to a family of toxins characterized as potent bioactive agents. These toxins have been involved in numerous aspects of cell pathophysiology including inflammatory response, platelet aggregation, endothelial cell hyperactivation, renal disorders, and hemolysis. The molecular mechanism by which these toxins cause hemolysis is under investigation; literature data have suggested that enzyme catalysis is necessary for the biological activities triggered by the toxin. However, the way by which phospholipase\u2010D activity is directly related with human hemolysis has not been determined. To evaluate how brown spider venom phospholipase\u2010D activity causes hemolysis, we examined the impact of recombinant phospholipase\u2010D on human red blood cells. Using six different purified recombinant phospholipase\u2010D molecules obtained from a cDNA venom gland library, we demonstrated that there is a correlation of hemolytic effect and phospholipase\u2010D activity. Studying recombinant phospholipase\u2010D, a potent hemolytic and phospholipase\u2010D recombinant toxin (LiRecDT1), we determined that the toxin degrades synthetic sphingomyelin (SM),\n                    <jats:italic>lyso<\/jats:italic>\n                    phosphatidylcholine (LPC), and\n                    <jats:italic>lyso<\/jats:italic>\n                    \u2010platelet\u2010activating factor. Additionally, we determined that the toxin degrades phospholipids in a detergent extract of human erythrocytes, as well as phospholipids from ghosts of human red blood cells. The products of the degradation of synthetic SM and LPC following recombinant phospholipase\u2010D treatments caused hemolysis of human erythrocytes. This hemolysis, dependent on products of metabolism of phospholipids, is also dependent on calcium ion concentration because the percentage of hemolysis increased with an increase in the dose of calcium in the medium. Recombinant phospholipase\u2010D treatment of human erythrocytes stimulated an influx of calcium into the cells that was detected by a calcium\u2010sensitive fluorescent probe (Fluo\u20104). This calcium influx was shown to be channel\u2010mediated rather than leak\u2010promoted because the influx was inhibited by L\u2010type calcium channel inhibitors but not by a T\u2010type calcium channel blocker, sodium channel inhibitor or a specific inhibitor of calcium activated potassium channels. Finally, this inhibition of hemolysis following recombinant phospholipase\u2010D treatment occurred in a concentration\u2010dependent manner in the presence of L\u2010type calcium channel blockers such as nifedipine and verapamil. The data provided herein, suggest that the brown spider venom phospholipase\u2010D\u2010induced hemolysis of human erythrocytes is dependent on the metabolism of membrane phospholipids, such as SM and LPC, generating bioactive products that stimulate a calcium influx into red blood cells mediated by the L\u2010type channel. J. Cell. Biochem. 112: 2529\u20132540, 2011. \u00a9 2011 Wiley\u2010Liss, Inc.\n                  <\/jats:p>","DOI":"10.1002\/jcb.23177","type":"journal-article","created":{"date-parts":[[2011,5,16]],"date-time":"2011-05-16T11:10:11Z","timestamp":1305544211000},"page":"2529-2540","source":"Crossref","is-referenced-by-count":48,"title":["The relationship between calcium and the metabolism of plasma membrane phospholipids in hemolysis induced by brown spider venom phospholipase\u2010D toxin"],"prefix":"10.1002","volume":"112","author":[{"given":"Daniele","family":"Chaves\u2010Moreira","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda N.","family":"Souza","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalvo T.H.","family":"Foga\u00e7a","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oldemir 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