Expression of phospholemman and its association with Na+-K+-ATPase in skeletal muscle: effects of aging and exercise training.
Phospholemman (PLM) is a recently identified accessory protein of the Na(+)-K(+)-ATPase (NKA), with a high level of expression in skeletal muscle. The objectives of this study are to characterize the PLM in skeletal muscle and to test the hypothesis that, as an accessory protein of NKA, expression of PLM and its association with the alpha-subunits of NKA is regulated during aging and with exercise training. PLM was characterized in skeletal muscle of 6- and 16-mo-old sedentary middle-aged rats (Ms), and the effects of aging and exercise training were studied in Ms, 29-mo-old sedentary senescent, and 29-mo-old treadmill-exercised senescent rats. Expression of PLM was muscle-type dependent, and immunofluorescence study showed that PLM distributed predominantly on the sarcolemmal membrane of the muscle fibers. Anti-PLM antibody reduced activity of NKA, and thus PLM appears to be required for NKA to express its full activity in skeletal muscle. Expression of PLM was not altered with aging but increased after exercise training. Coimmunoprecipitation studies demonstrated that PLM associates with both the alpha(1)- and alpha(2)-subunit isoforms of NKA. Compared with Ms rats, levels of PLM-associated alpha(1)-subunit increased in 29-mo-old sedentary senescent rats, and treadmill exercise has a tendency to partially reverse it. There was no significant change in PLM-associated alpha(2)-subunit with age, and exercise training has a tendency to increase that level. It is concluded that, in skeletal muscle, PLM appears to be a protein integral to the NKA complex and that PLM has the potential to modulate NKA in an isoform-specific and muscle type-dependent manner in aging and after exercise training.
Reis
Justin
J
Deparment of Pharmacology, The Milton S. Hershey Medical Center, College of Medicine, The Pennsylvania State University, 17033, USA.
Zhang
Lianqin
L
Cala
Steve
S
Jew
Korinne N
KN
Mace
Lisa C
LC
Chung
Linda
L
Moore
Russell L
RL
Ng
Yuk-Chow
YC
D000375:Aging / Q000378:metabolism*; D000818:Animals; D005455:Fluorescent Antibody Technique; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D008565:Membrane Proteins; D010750:Phosphoproteins; C069141:phospholemman; D000254:Sodium-Potassium-Exchanging ATPase