Titin, myosin light chains and C-protein in the developing and failing human heart.
We investigated relative amounts of titin, myosin light chains (MLC), C-protein, and myosin heavy chains (MHC) in the functionally intact contractile apparatus of embryonic, adult normal, and adult failing human left ventricle by SDS polyacrylamide gel electrophoresis and Western blot analysis. The amount of titin and the titin-MHC ratio was significantly (P < 0.05) lower in the embryonic and adult failing human compared to the adult normal fibres. Additionally, we found a protein band having a lower molecular weight but the same immunoreactivity as native titin (fast-migrating titin; FM-titin) in the failing heart only. The MLC-1/MLC-2 ratio was about 1.0 in normal and failing hearts but about 2.0 in the embryonic heart. Relative amount of C-protein was the same in normal and failing fibres but lower in the embryonic ventricles. Length-tension ratio of chemically skinned fibres prepared from terminally failing hearts was impaired compared to normal heart fibres. We conclude that both the reduced titin/MHC ratio and the expression of a structurally different titin form may be involved in the impaired contractile function of the terminally failing human heart.
Max Delbrück Centre for Molecular Medicine, Berlin-Buch, Germany.
I
I
Morano
K
K
Hädicke
S
S
Grom
A
A
Koch
R H
RH
Schwinger
M
M
Böhm
S
S
Bartel
E
E
Erdmann
E G
EG
Krause
D002352:Carrier Proteins; D064211:Connectin; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006321:Heart / Q000196:embryology / Q000254:growth & development*; D006333:Heart Failure / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000378:metabolism*; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009218:Myosins / Q000378:metabolism*; D011494:Protein Kinases; D000099163:Myosin Binding Protein C
D002352:Carrier Proteins; D064211:Connectin; D009124:Muscle Proteins; D009218:Myosins; D011494:Protein Kinases; D000099163:Myosin Binding Protein C; C577285:TTN protein, human