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Disease
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Drug
Enzyme
Compound
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Gene/Protein
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Drug
Enzyme
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Target Concepts:
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Query: UMLS:C0155339 (
Brown
)
12,436
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Previous studies showed increased
phospholemman
(
PLM
) mRNA after myocardial infarction (MI) in rats (Sehl PD, Tai JTN, Hillan KJ,
Brown
LA, Goddard A, Yang R, Jin H, and Lowe DG. Circulation 101: 1990-1999, 2000). We tested the hypothesis that, in normal adult rat cardiac myocytes,
PLM
overexpression alters contractile function and cytosolic Ca(2+) concentration ([Ca(2+)](i)) homeostasis in a manner similar to that observed in post-MI myocytes. Compared with myocytes infected by control adenovirus expressing green fluorescent protein (GFP) alone, Western blots indicated a 41% increase in
PLM
expression after 72 h (P < 0.001) but no changes in Na(+)/Ca(2+) exchanger, SERCA2, and calsequestrin levels in myocytes infected by adenovirus expressing GFP and
PLM
. At 5 mM extracellular [Ca(2+)] ([Ca(2+)](o)), maximal contraction amplitudes in
PLM
-overexpressed myocytes were 24% (P < 0.005) and [Ca(2+)](i) transient amplitudes were 18% (P < 0.05) lower than control myocytes. At 0.6 mM [Ca(2+)](o), however, contraction and [Ca(2+)](i) transient amplitudes were significantly (P < 0.05) higher in
PLM
-overexpressed than control myocytes (18% and 42%, respectively); at 1.8 mM [Ca(2+)](o), the differences in contraction and [Ca(2+)](i) transient amplitudes were narrowed. This pattern of contractile and [Ca(2+)](i) transient abnormalities in
PLM
-overexpressed myocytes mimics that observed in post-MI rat myocytes. We suggest that
PLM
overexpression observed in post-MI myocytes may partly account for contractile abnormalities by perturbing Ca(2+) fluxes during excitation-contraction.
...
PMID:Overexpression of phospholemman alters contractility and [Ca(2+)](i) transients in adult rat myocytes. 1212 4