Cyclosporin A preferentially attenuates skeletal slow-twitch muscle regeneration

Calcineurin, a Ca2+/calmodulin-dependent phosphatase, is associated with muscle regeneration via NFATc1/GATA2-dependent pathways. However, it is not clear whether calcineurin preferentially affects the regeneration of slow- or fast-twitch muscles. We investigated the effect of a calcineurin inhibito...

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Main Authors: Miyabara E.H., Aoki M.S., Moriscot A.S.
Format: Article
Language:English
Published: Associação Brasileira de Divulgação Científica 2005-01-01
Series:Brazilian Journal of Medical and Biological Research
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005000400009
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author Miyabara E.H.
Aoki M.S.
Moriscot A.S.
author_facet Miyabara E.H.
Aoki M.S.
Moriscot A.S.
author_sort Miyabara E.H.
collection DOAJ
description Calcineurin, a Ca2+/calmodulin-dependent phosphatase, is associated with muscle regeneration via NFATc1/GATA2-dependent pathways. However, it is not clear whether calcineurin preferentially affects the regeneration of slow- or fast-twitch muscles. We investigated the effect of a calcineurin inhibitor, cyclosporin A (CsA), on the morphology and fiber diameter of regenerating slow- and fast-twitch muscles. Adult Wistar rats (259.5 ± 9 g) maintained under standard conditions were treated with CsA (20 mg/kg body weight, ip) for 5 days, submitted to cryolesion of soleus and tibialis anterior (TA) muscles on the 6th day, and then treated with CsA for an additional 21 days. The muscles were removed, weighed, frozen, and stored in liquid nitrogen. Cryolesion did not alter the body weight gain of the animals after 21 days of regeneration (P = 0.001) and CsA significantly reduced the body weight gain (15.5%; P = 0.01) during the same period. All treated TA and soleus muscles showed decreased weights (17 and 29%, respectively, P < 0.05). CsA treatment decreased the cross-sectional area of both soleus and TA muscles of cryoinjured animals (TA: 2108 ± 930 vs 792 ± 640 µm²; soleus: 2209 ± 322 vs 764 ± 439 m²; P < 0.001). Histological sections of both muscles stained with Toluidine blue revealed similar regenerative responses after cryolesion. In addition, CsA was able to minimize these responses, i.e., centralized nuclei and split fibers, more efficiently so in TA muscle. These results indicate that calcineurin preferentially plays a role in regeneration of slow-twitch muscle.
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spelling doaj.art-10fe7130314a4a71825a0895257a67952022-12-21T22:21:30ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X0034-73102005-01-01384559563Cyclosporin A preferentially attenuates skeletal slow-twitch muscle regenerationMiyabara E.H.Aoki M.S.Moriscot A.S.Calcineurin, a Ca2+/calmodulin-dependent phosphatase, is associated with muscle regeneration via NFATc1/GATA2-dependent pathways. However, it is not clear whether calcineurin preferentially affects the regeneration of slow- or fast-twitch muscles. We investigated the effect of a calcineurin inhibitor, cyclosporin A (CsA), on the morphology and fiber diameter of regenerating slow- and fast-twitch muscles. Adult Wistar rats (259.5 ± 9 g) maintained under standard conditions were treated with CsA (20 mg/kg body weight, ip) for 5 days, submitted to cryolesion of soleus and tibialis anterior (TA) muscles on the 6th day, and then treated with CsA for an additional 21 days. The muscles were removed, weighed, frozen, and stored in liquid nitrogen. Cryolesion did not alter the body weight gain of the animals after 21 days of regeneration (P = 0.001) and CsA significantly reduced the body weight gain (15.5%; P = 0.01) during the same period. All treated TA and soleus muscles showed decreased weights (17 and 29%, respectively, P < 0.05). CsA treatment decreased the cross-sectional area of both soleus and TA muscles of cryoinjured animals (TA: 2108 ± 930 vs 792 ± 640 µm²; soleus: 2209 ± 322 vs 764 ± 439 m²; P < 0.001). Histological sections of both muscles stained with Toluidine blue revealed similar regenerative responses after cryolesion. In addition, CsA was able to minimize these responses, i.e., centralized nuclei and split fibers, more efficiently so in TA muscle. These results indicate that calcineurin preferentially plays a role in regeneration of slow-twitch muscle.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005000400009CalcineurinCyclosporin ARegenerationFast and slow twitch muscles
spellingShingle Miyabara E.H.
Aoki M.S.
Moriscot A.S.
Cyclosporin A preferentially attenuates skeletal slow-twitch muscle regeneration
Brazilian Journal of Medical and Biological Research
Calcineurin
Cyclosporin A
Regeneration
Fast and slow twitch muscles
title Cyclosporin A preferentially attenuates skeletal slow-twitch muscle regeneration
title_full Cyclosporin A preferentially attenuates skeletal slow-twitch muscle regeneration
title_fullStr Cyclosporin A preferentially attenuates skeletal slow-twitch muscle regeneration
title_full_unstemmed Cyclosporin A preferentially attenuates skeletal slow-twitch muscle regeneration
title_short Cyclosporin A preferentially attenuates skeletal slow-twitch muscle regeneration
title_sort cyclosporin a preferentially attenuates skeletal slow twitch muscle regeneration
topic Calcineurin
Cyclosporin A
Regeneration
Fast and slow twitch muscles
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2005000400009
work_keys_str_mv AT miyabaraeh cyclosporinapreferentiallyattenuatesskeletalslowtwitchmuscleregeneration
AT aokims cyclosporinapreferentiallyattenuatesskeletalslowtwitchmuscleregeneration
AT moriscotas cyclosporinapreferentiallyattenuatesskeletalslowtwitchmuscleregeneration