Calcineurin has been proposed to regulate skeletal muscle hypertrophy, while its relevance to the pathogenesis of muscle atrophy is unknown. The present study was aimed to investigate if perturbations of the calcineurin pathway may be involved in causing skeletal muscle atrophy in two different experimental conditions: cancer cachexia (rats bearing the AH-130 hepatoma), and hyperglycemia (rats treated with streptozotocin). Calcineurin expression in the gastrocnemius was comparable between tumor hosts and controls. By contrast, besides unchanged calcineurin mRNA levels, those of protein were lower in diabetic animals than in controls. The DNA-binding activity of the transcription factors NF-AT and MEF-2 was analysed as an indirect measure of calcineurin activity in vivo. The nuclear translocation of both factors was similar in tumor hosts and controls. Consistently with the reduced calcineurin protein levels, NF-AT DNA-binding activity significantly decreased in the gastrocnemius of diabetic rats compared to controls. Finally, muscle wasting correction afforded in the AH-130 hosts by pentoxifylline or interleukin-15 was not paralleled by changes of calcineurin mRNA levels, while treatment of diabetic animals with dehydroepiandrosterone partially prevented calcineurin down-regulation. These results suggest that modulations of calcineurin activity may be involved in the pathogenesis of muscle wasting in diabetes though not in cancer cachexia.

Modulations of the calcineurin/NF-AT pathway in skeletal muscle atrophy

COSTELLI, Paola;REFFO, Patrizia;PENNA, FABIO;ARAGNO, Manuela;MASTROCOLA, Raffaella;BOCCUZZI, Giuseppe;BONELLI, Gabriella;BACCINO, Francesco Maria
2007-01-01

Abstract

Calcineurin has been proposed to regulate skeletal muscle hypertrophy, while its relevance to the pathogenesis of muscle atrophy is unknown. The present study was aimed to investigate if perturbations of the calcineurin pathway may be involved in causing skeletal muscle atrophy in two different experimental conditions: cancer cachexia (rats bearing the AH-130 hepatoma), and hyperglycemia (rats treated with streptozotocin). Calcineurin expression in the gastrocnemius was comparable between tumor hosts and controls. By contrast, besides unchanged calcineurin mRNA levels, those of protein were lower in diabetic animals than in controls. The DNA-binding activity of the transcription factors NF-AT and MEF-2 was analysed as an indirect measure of calcineurin activity in vivo. The nuclear translocation of both factors was similar in tumor hosts and controls. Consistently with the reduced calcineurin protein levels, NF-AT DNA-binding activity significantly decreased in the gastrocnemius of diabetic rats compared to controls. Finally, muscle wasting correction afforded in the AH-130 hosts by pentoxifylline or interleukin-15 was not paralleled by changes of calcineurin mRNA levels, while treatment of diabetic animals with dehydroepiandrosterone partially prevented calcineurin down-regulation. These results suggest that modulations of calcineurin activity may be involved in the pathogenesis of muscle wasting in diabetes though not in cancer cachexia.
2007
1770
1028
1036
Costelli P.; Almendro V.; Figueras M.T.; Reffo P.; Penna F.; Aragno M; Mastrocola R; Boccuzzi G; Busquets S; Bonelli G; Lopez F.J; Argilés J.M.; Bacci...espandi
File in questo prodotto:
File Dimensione Formato  
15)BBA2007.pdf

Accesso riservato

Tipo di file: PDF EDITORIALE
Dimensione 637.36 kB
Formato Adobe PDF
637.36 kB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/57733
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 9
  • ???jsp.display-item.citation.isi??? 8
social impact