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Contractions activate hormone-sensitive lipase in rat muscle by protein kinase C and mitogen-activated protein kinase

Donsmark, M; Langfort, J; Holm, Cecilia LU ; Ploug, T and Galbo, H (2003) In Journal of Physiology 550(3). p.845-854
Abstract
Intramuscular triacylglycerol is an important energy store and is also related to insulin resistance. The mobilization of fatty acids from this pool is probably regulated by hormone-sensitive lipase (HSL), which has recently been shown to exist in muscle and to be activated by both adrenaline and contractions. Adrenaline acts via cAMP-dependent protein kinase (PKA). The signalling mediating the effect of contractions is unknown and was explored in this study. Incubated soleus muscles from 70 g male rats were electrically stimulated to perform repeated tetanic contractions for 5 min. The contraction-induced activation of HSL was abolished by the protein kinase C (PKC) inhibitors bisindolylmaleimide I and calphostin C and reduced 50 % by the... (More)
Intramuscular triacylglycerol is an important energy store and is also related to insulin resistance. The mobilization of fatty acids from this pool is probably regulated by hormone-sensitive lipase (HSL), which has recently been shown to exist in muscle and to be activated by both adrenaline and contractions. Adrenaline acts via cAMP-dependent protein kinase (PKA). The signalling mediating the effect of contractions is unknown and was explored in this study. Incubated soleus muscles from 70 g male rats were electrically stimulated to perform repeated tetanic contractions for 5 min. The contraction-induced activation of HSL was abolished by the protein kinase C (PKC) inhibitors bisindolylmaleimide I and calphostin C and reduced 50 % by the mitogen-activated protein kinase kinase (MEK) inhibitor U0126, which also completely blocked extracellular signal-regulated kinase (ERK) 1 and 2 phosphorylation. None of the inhibitors reduced adrenaline-induced HSL activation in soleus muscle. Both phorbol-12-myristate-13-acetate (PMA), which activates PKC and, in turn, ERK, and caffeine, which increases intracellular Ca2+ without eliciting contraction, increased HSL activity. Activated ERK increased HSL activity in supernatant from basal but not from electrically stimulated muscle. In conclusion, in muscle, PKC can stimulate HSL through ERK. Contractions and adrenaline enhance muscle HSL activity by different signalling mechanisms. The effect of contractions is mediated by PKC, at least partly via the ERK pathway. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Physiology
volume
550
issue
3
pages
845 - 854
publisher
The Physiological Society
external identifiers
  • pmid:12794177
  • wos:000185005100015
  • scopus:0041473899
ISSN
1469-7793
DOI
10.1113/jphysiol.2003.042333
language
English
LU publication?
yes
id
937a9297-9a3e-45f4-990e-404679430484 (old id 302212)
date added to LUP
2007-08-29 12:16:31
date last changed
2017-09-24 04:34:08
@article{937a9297-9a3e-45f4-990e-404679430484,
  abstract     = {Intramuscular triacylglycerol is an important energy store and is also related to insulin resistance. The mobilization of fatty acids from this pool is probably regulated by hormone-sensitive lipase (HSL), which has recently been shown to exist in muscle and to be activated by both adrenaline and contractions. Adrenaline acts via cAMP-dependent protein kinase (PKA). The signalling mediating the effect of contractions is unknown and was explored in this study. Incubated soleus muscles from 70 g male rats were electrically stimulated to perform repeated tetanic contractions for 5 min. The contraction-induced activation of HSL was abolished by the protein kinase C (PKC) inhibitors bisindolylmaleimide I and calphostin C and reduced 50 % by the mitogen-activated protein kinase kinase (MEK) inhibitor U0126, which also completely blocked extracellular signal-regulated kinase (ERK) 1 and 2 phosphorylation. None of the inhibitors reduced adrenaline-induced HSL activation in soleus muscle. Both phorbol-12-myristate-13-acetate (PMA), which activates PKC and, in turn, ERK, and caffeine, which increases intracellular Ca2+ without eliciting contraction, increased HSL activity. Activated ERK increased HSL activity in supernatant from basal but not from electrically stimulated muscle. In conclusion, in muscle, PKC can stimulate HSL through ERK. Contractions and adrenaline enhance muscle HSL activity by different signalling mechanisms. The effect of contractions is mediated by PKC, at least partly via the ERK pathway.},
  author       = {Donsmark, M and Langfort, J and Holm, Cecilia and Ploug, T and Galbo, H},
  issn         = {1469-7793},
  language     = {eng},
  number       = {3},
  pages        = {845--854},
  publisher    = {The Physiological Society},
  series       = {Journal of Physiology},
  title        = {Contractions activate hormone-sensitive lipase in rat muscle by protein kinase C and mitogen-activated protein kinase},
  url          = {http://dx.doi.org/10.1113/jphysiol.2003.042333},
  volume       = {550},
  year         = {2003},
}