Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin
On the basis of our report that a glycolipoprotein fraction (GLP) extracted from Leptospira interrogans contains a potent inhibitor of renal Na,K-ATPase, we proposed that GLP-induced inhibition of Na,K-ATPase might be the primary cellular defect in the physiopathology of leptospirosis. The present s...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
1997-01-01
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| Series: | Brazilian Journal of Medical and Biological Research |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1997000200009 |
| _version_ | 1819206416937779200 |
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| author | Younes-Ibrahim M. Buffin-Meyer B. Cheval L. Burth P. Castro-Faria M.V. Barlet-Bas C. Marsy S. Doucet A. |
| author_facet | Younes-Ibrahim M. Buffin-Meyer B. Cheval L. Burth P. Castro-Faria M.V. Barlet-Bas C. Marsy S. Doucet A. |
| author_sort | Younes-Ibrahim M. |
| collection | DOAJ |
| description | On the basis of our report that a glycolipoprotein fraction (GLP) extracted from Leptospira interrogans contains a potent inhibitor of renal Na,K-ATPase, we proposed that GLP-induced inhibition of Na,K-ATPase might be the primary cellular defect in the physiopathology of leptospirosis. The present study was designed to test this hypothesis by determining whether or not 1) GLP inhibits all the isoforms of Na,K-ATPase which are expressed in the tissues affected by leptospirosis, 2) Na,K-ATPase from leptospirosis-resistant species, such as the rat, is sensitive to GLP, 3) GLP inhibits Na,K-ATPase from intact cells, and 4) GLP inhibits ouabain-sensitive H,K-ATPase. The results indicate that in the rabbit, a leptospirosis-sensitive species, GLP inhibits with similar efficiency (apparent IC50: 120-220 µg protein GLP/ml) all isoforms of Na,K-ATPase known to be expressed in target tissues for the disease. Na,K-ATPase from rat kidney displays a sensitivity to GLP similar to that of the rabbit kidney enzyme (apparent IC50: 25-80 and 50-150 µg protein GLP/ml for rat and rabbit, respectively), indicating that resistance to the disease does not result from the resistance of Na,K-ATPase to GLP. GLP also reduces ouabain-sensitive rubidium uptake in rat thick ascending limbs (pmol mm-1 min-1 ± SEM; control: 23.8 ± 1.8; GLP, 88 µg protein/ml: 8.2 ± 0.9), demonstrating that it is active in intact cells. Finally, GLP had no demonstrable effect on renal H,K-ATPase activity, even on the ouabain-sensitive form, indicating that the active principle of GLP is more specific for Na,K-ATPase than ouabain itself. Although the hypothesis remains to be demonstrated in vivo, the present findings are compatible with the putative role of GLP-induced inhibition of Na,K-ATPase as an initial mechanism in the physiopathology of leptospirosis |
| first_indexed | 2024-12-23T05:07:16Z |
| format | Article |
| id | doaj.art-29bef6a6789e470280715688101bd983 |
| institution | Directory Open Access Journal |
| issn | 0100-879X 0034-7310 |
| language | English |
| last_indexed | 2024-12-23T05:07:16Z |
| publishDate | 1997-01-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-29bef6a6789e470280715688101bd9832022-12-21T17:59:02ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X0034-73101997-01-01302213223Na,K-ATPase: a molecular target for Leptospira interrogans endotoxinYounes-Ibrahim M.Buffin-Meyer B.Cheval L.Burth P.Castro-Faria M.V.Barlet-Bas C.Marsy S.Doucet A.On the basis of our report that a glycolipoprotein fraction (GLP) extracted from Leptospira interrogans contains a potent inhibitor of renal Na,K-ATPase, we proposed that GLP-induced inhibition of Na,K-ATPase might be the primary cellular defect in the physiopathology of leptospirosis. The present study was designed to test this hypothesis by determining whether or not 1) GLP inhibits all the isoforms of Na,K-ATPase which are expressed in the tissues affected by leptospirosis, 2) Na,K-ATPase from leptospirosis-resistant species, such as the rat, is sensitive to GLP, 3) GLP inhibits Na,K-ATPase from intact cells, and 4) GLP inhibits ouabain-sensitive H,K-ATPase. The results indicate that in the rabbit, a leptospirosis-sensitive species, GLP inhibits with similar efficiency (apparent IC50: 120-220 µg protein GLP/ml) all isoforms of Na,K-ATPase known to be expressed in target tissues for the disease. Na,K-ATPase from rat kidney displays a sensitivity to GLP similar to that of the rabbit kidney enzyme (apparent IC50: 25-80 and 50-150 µg protein GLP/ml for rat and rabbit, respectively), indicating that resistance to the disease does not result from the resistance of Na,K-ATPase to GLP. GLP also reduces ouabain-sensitive rubidium uptake in rat thick ascending limbs (pmol mm-1 min-1 ± SEM; control: 23.8 ± 1.8; GLP, 88 µg protein/ml: 8.2 ± 0.9), demonstrating that it is active in intact cells. Finally, GLP had no demonstrable effect on renal H,K-ATPase activity, even on the ouabain-sensitive form, indicating that the active principle of GLP is more specific for Na,K-ATPase than ouabain itself. Although the hypothesis remains to be demonstrated in vivo, the present findings are compatible with the putative role of GLP-induced inhibition of Na,K-ATPase as an initial mechanism in the physiopathology of leptospirosishttp://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1997000200009Na/K-ATPaseH/K-ATPaseNa/K-ATPase isoformsRubidium transportLeptospirosisOuabain |
| spellingShingle | Younes-Ibrahim M. Buffin-Meyer B. Cheval L. Burth P. Castro-Faria M.V. Barlet-Bas C. Marsy S. Doucet A. Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin Brazilian Journal of Medical and Biological Research Na/K-ATPase H/K-ATPase Na/K-ATPase isoforms Rubidium transport Leptospirosis Ouabain |
| title | Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin |
| title_full | Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin |
| title_fullStr | Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin |
| title_full_unstemmed | Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin |
| title_short | Na,K-ATPase: a molecular target for Leptospira interrogans endotoxin |
| title_sort | na k atpase a molecular target for leptospira interrogans endotoxin |
| topic | Na/K-ATPase H/K-ATPase Na/K-ATPase isoforms Rubidium transport Leptospirosis Ouabain |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X1997000200009 |
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