PMID- 23202294
OWN - NLM
STAT- MEDLINE
DCOM- 20130306
LR  - 20211021
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Linking)
VI  - 19
IP  - 1
DP  - 2013 Jan
TI  - Activation of calcium signaling through Trpv1 by nNOS and peroxynitrite as a key 
      trigger of skeletal muscle hypertrophy.
PG  - 101-6
LID - 10.1038/nm.3019 [doi]
AB  - Skeletal muscle atrophy occurs in aging and pathological conditions, including 
      cancer, diabetes and AIDS. Treatment of atrophy is based on either preventing 
      protein-degradation pathways, which are activated during atrophy, or activating 
      protein-synthesis pathways, which induce muscle hypertrophy. Here we show that 
      neuronal nitric oxide synthase (nNOS) regulates load-induced hypertrophy by 
      activating transient receptor potential cation channel, subfamily V, member 1 
      (TRPV1). The overload-induced hypertrophy was prevented in nNOS-null mice. nNOS 
      was transiently activated within 3 min after overload. This activation promoted 
      formation of peroxynitrite, a reaction product of nitric oxide with superoxide, 
      which was derived from NADPH oxidase 4 (Nox4). Nitric oxide and peroxynitrite 
      then activated Trpv1, resulting in an increase of intracellular Ca(2+) 
      concentration ([Ca(2+)](i)) that subsequently triggered activation of mammalian 
      target of rapamycin (mTOR). Notably, administration of the TRPV1 agonist 
      capsaicin induced hypertrophy without overload and alleviated unloading- or 
      denervation-induced atrophy. These findings identify nitric oxide, peroxynitrite 
      and [Ca(2+)](i) as the crucial mediators that convert a mechanical load into an 
      intracellular signaling pathway and lead us to suggest that TRPV1 could be a new 
      therapeutic target for treating muscle atrophy.
FAU - Ito, Naoki
AU  - Ito N
AD  - Department of Molecular Therapy, National Institute of Neuroscience, National 
      Center of Neurology and Psychiatry, Kodaira, Japan.
FAU - Ruegg, Urs T
AU  - Ruegg UT
FAU - Kudo, Akira
AU  - Kudo A
FAU - Miyagoe-Suzuki, Yuko
AU  - Miyagoe-Suzuki Y
FAU - Takeda, Shin'ichi
AU  - Takeda S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121202
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Antipruritics)
RN  - 0 (TRPV Cation Channels)
RN  - 0 (TRPV1 protein, mouse)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type I)
RN  - EC 1.14.13.39 (Nos1 protein, mouse)
RN  - EC 1.6.3.- (NADPH Oxidase 4)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 1.6.3.- (Nox4 protein, mouse)
RN  - S07O44R1ZM (Capsaicin)
RN  - SY7Q814VUP (Calcium)
SB  - IM
CIN - Channels (Austin). 2013 May-Jun;7(3):221-4. PMID: 23584166
MH  - Animals
MH  - Antipruritics/pharmacology
MH  - Calcium/analysis
MH  - *Calcium Signaling/drug effects
MH  - Capsaicin/pharmacology
MH  - Cell Line
MH  - Hindlimb Suspension
MH  - Hypertrophy/metabolism/pathology
MH  - Ion Transport/drug effects
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Muscle, Skeletal/metabolism/*pathology
MH  - NADPH Oxidase 4
MH  - NADPH Oxidases/metabolism
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type I/*metabolism
MH  - Peroxynitrous Acid/*metabolism
MH  - Signal Transduction/drug effects
MH  - TRPV Cation Channels/*metabolism
EDAT- 2012/12/04 06:00
MHDA- 2013/03/07 06:00
CRDT- 2012/12/04 06:00
PHST- 2012/03/01 00:00 [received]
PHST- 2012/11/01 00:00 [accepted]
PHST- 2012/12/04 06:00 [entrez]
PHST- 2012/12/04 06:00 [pubmed]
PHST- 2013/03/07 06:00 [medline]
AID - nm.3019 [pii]
AID - 10.1038/nm.3019 [doi]
PST - ppublish
SO  - Nat Med. 2013 Jan;19(1):101-6. doi: 10.1038/nm.3019. Epub 2012 Dec 2.