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LiCl causes an acute decrease in ataxia telangiectasia mutated (ATM) protein levels in L6 myotubes
Author(s) -
RobinsonHill Rona,
Ching James Kain,
Fisher Jonathan S.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.lb675
Subject(s) - myogenesis , ampk , protein kinase a , endocrinology , chemistry , medicine , amp activated protein kinase , skeletal muscle , kinase , biology , biochemistry
We have previously found that insulin‐like growth factor 1 (IGF‐1) causes an acute increase in levels of ATM in cultured myotubes and in mouse skeletal muscle and that serum starvation (SS) of myotubes causes concomitant increases in levels of the AMP‐activated protein kinase (AMPK) and ATM. Here, we show the validity of the SS effect on increase of ATM by running negative and positive controls for ATM and showing that ATM runs at the appropriate molecular weight (~350 kDa, between 460 kDa and 268 kDa markers). To determine the potential role of AMPK in the SS effect on ATM protein levels, we transduced L6 myotubes with either green fluorescent protein (GFP) or a dominant negative form of AMPK (AMPK‐DN). SS increased ATM protein levels by more than 2‐fold (P<0.05, n=6/group) in myotubes expressing GFP but not in myotubes expressing AMPK‐DN. Because IGF‐1 and AMPK both inhibit glycogen synthase kinase 3β (GSK3β), we hypothesized that the GSK3β inhibitor Li + would cause an increase in ATM levels. Contrary to our hypothesis, one hour of incubation of L6 myotubes with 1 mM LiCl caused about a 50% decrease (P<0.05, n=12/group) in ATM protein levels compared to a 1 mM NaCl control. Thus, it appears that inhibition of GSK3β causes an acute decrease in ATM protein levels, and AMPK and IGF‐1 act through a GSK3β‐independent pathway to increase ATM protein levels.