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Downregulation Of SERCA Pump Expression In The Rat Diaphragm After Corticosteroid Treatment

Gayan-Ramirez, G. (Laboratory of Pneumology, Katholieke Universiteit Leuven, Belgium)
Vanzeir, L. (Laboratory of Pneumology, Katholieke Universiteit Leuven, Belgium)
Decramer, M. (Laboratory of Pneumology, Katholieke Universiteit Leuven, Belgium)
Wuytack, F. (Laboratory of Physiology, Katholieke Universiteit Leuven, Belgium)

Contact Person: Ghislaine Gayan-Ramirez (ghislaine.gayan-ramirez@med.kuleuven.ac.be)


Acute myopathy often develops after short-term treatment with massive doses of corticosteroids as given to patients to treat status asthmaticus or to prevent rejection after lung transplantation. We previously demonstrated that corticosteroid treatment (80mg/kg triamcinolone daily during 5 days) resulted in a selective type II fiber atrophy (cross-sectional area type IIa fibers: -19% and IIx/b fibers: -30%) and a prolongation of the half-relaxation time (25+/-4 vs 21+/-4 msec, p < 0.05) in the rat diaphragm (1). Since calcium re-uptake is essential for muscle relaxation, the relative expression of the three SERCA isoforms and phospholamban was measured by RT-PCR in the diaphragm of controls and triamcinolone-treated rats (n=8/group). Triamcinolone treatment reduced SERCA1+2 levels by 70% compared to controls (p < 0.05). This reduction resulted from a decrease in both SERCA1 (-69%, p < 0.05) and SERCA2 (-49%, NS). Moreover, the SERCA2 relative proportion was increased from 43+/-7% in control diaphragm to 52+/-4% after triamcinolone (p < 0.05). Phospholamban expression was also reduced (-31%, NS) as were SERCA2a levels (-40%, p < 0.05). Only SERCA1a was found in the diaphragm while SERCA1b, SERCA2b and SERCA3 fell below the detection limit. We conclude that prolonged half-relaxation time observed after corticosteroid treatment is probably related to alterations in SERCA pumps and mainly to decreased SERCA1 relative expression. The latter is in agreement with the selective type II fiber atrophy seen in the diaphragm of triamcinolone-treated rats. (Supported by the 'Fonds voor Wetenschappelijk Onderzoek-Vlaanderen, grants # 3.0167.95 and # G. 0189.97 and Astra Pharmaceuticals). (1) Nava et al. AJRCCM 1996; 153: 1888-96.

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Poster Number PAgayan-ramirez0369
Keywords: Diaphragm, SERCA, Corticosteroids

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Gayan-Ramirez, G.; Vanzeir, L.; Decramer, M.; Wuytack, F.; (1998). Downregulation Of SERCA Pump Expression In The Rat Diaphragm After Corticosteroid Treatment. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Available at URL http://www.mcmaster.ca/inabis98/cellbio/gayan-ramirez0369/index.html
© 1998 Author(s) Hold Copyright