scholarly journals The Ku Protein Complex Interacts with YY1, Is Up-Regulated in Human Heart Failure, and Represses α Myosin Heavy-Chain Gene Expression

2004 ◽  
Vol 24 (19) ◽  
pp. 8705-8715 ◽  
Author(s):  
Carmen C. Sucharov ◽  
Steve M. Helmke ◽  
Stephen J. Langer ◽  
M. Benjamin Perryman ◽  
Michael Bristow ◽  
...  
Keyword(s):  
Heart Failure ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Human Heart ◽  
Ventricular Myocytes ◽  
Major Effect ◽  
Neonatal Rat ◽  
Chain Gene ◽  
Human Heart Failure ◽  
Peptide Mass

ABSTRACT Human heart failure is accompanied by repression of genes such as α myosin heavy chain (αMyHC) and SERCA2A and the induction of fetal genes such as βMyHC and atrial natriuretic factor. It seems likely that changes in MyHC isoforms contribute to the poor contractility seen in heart failure, because small changes in isoform composition can have a major effect on the contractility of cardiac myocytes and the heart. Our laboratory has recently shown that YY1 protein levels are increased in human heart failure and that YY1 represses the activity of the human αMyHC promoter. We have now identified a region of the αMyHC promoter that binds a factor whose expression is increased sixfold in failing human hearts. Through peptide mass spectrometry, we identified this binding activity to be a heterodimer of Ku70 and Ku80. Expression of Ku represses the human αMyHC promoter in neonatal rat ventricular myocytes. Moreover, overexpression of Ku70/80 decreases αMyHC mRNA expression and increases skeletal α-actin. Interestingly, YY1 interacts with Ku70 and Ku80 in HeLa cells. Together, YY1, Ku70, and Ku80 repress the αMyHC promoter to an extent that is greater than that with YY1 or Ku70/80 alone. Our results suggest that Ku is an important factor in the repression of the human αMyHC promoter during heart failure.

scholarly journals Myosin heavy chain gene expression in human heart failure.

1997 ◽  
Vol 100 (9) ◽  
pp. 2362-2370 ◽  
Author(s):  
K Nakao ◽  
W Minobe ◽  
R Roden ◽  
M R Bristow ◽  
L A Leinwand
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Human Heart ◽  
Chain Gene ◽  
Heavy Chain Gene ◽  
Myosin Heavy Chain Gene ◽  
Human Heart Failure

scholarly journals Reduced Beta Myosin Heavy Chain K213 Acetylation and T215 Phosphorylation in Human Heart Failure

2020 ◽  
Vol 118 (3) ◽  
pp. 436a
Author(s):  
Amanda Wacker ◽  
Michelle C. Rodriguez Garcia ◽  
Maicon Landim Vieira ◽  
Rakesh K. Singh ◽  
Elizabeth A. Brundage ◽  
...  
Keyword(s):  
Heart Failure ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Human Heart ◽  
Human Heart Failure

scholarly journals Yin Yang 1 Is Increased in Human Heart Failure and Represses the Activity of the Human α-Myosin Heavy Chain Promoter

2003 ◽  
Vol 278 (33) ◽  
pp. 31233-31239 ◽  
Author(s):  
Carmen C. Sucharov ◽  
Peter Mariner ◽  
Carlin Long ◽  
Michael Bristow ◽  
Leslie Leinwand
Keyword(s):  
Heart Failure ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Human Heart ◽  
Human Heart Failure ◽  
Yin Yang 1 ◽  
Yin Yang

Myosin heavy chain turnover in cultured neonatal rat heart cells: effects of [Ca2+]i and contractile activity

1996 ◽  
Vol 271 (5) ◽  
pp. C1447-C1456 ◽  
Author(s):  
K. L. Byron ◽  
J. L. Puglisi ◽  
J. R. Holda ◽  
D. Eble ◽  
A. M. Samarel
Keyword(s):  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Protein Turnover ◽  
Ventricular Myocytes ◽  
Contractile Activity ◽  
Myofibrillar Protein ◽  
Neonatal Rat ◽  
Heart Cells ◽  
Cell Shortening ◽  
Rat Heart Cells

Blockade of L-type Ca2+ channels in spontaneously contracting cultured neonatal rat ventricular myocytes causes contractile arrest, myofibrillar disassembly, and accelerated myofibrillar protein turnover. To determine whether myofibrillar protein turnover. To determine whether myofibrillar atrophy results indirectly from loss of mechanical signals or directly from alterations in intracellular Ca2+ concentration ([Ca2+]i), contractile activity was inhibited with verapamil (10 microM) or 2,3-butanedione monoxime (BDM), and their effects on cell shortening, [Ca2+]i, and myosin heavy chain (MHC) turnover were assessed. Control cells demonstrated spontaneous [Ca2+]i transients (peak amplitude 232 +/- 15 nM, 1-2 Hz) and vigorous contractile activity. Verapamil inhibited shortening by eliminating spontaneous [Ca2+]i transients. Low concentrations of BDM (5.0-7.5 mM) had no effect on basal or peak [Ca2+]i transient amplitude but reduced cell shortening, whereas 10 mM BDM reduced both [Ca2+]i transient amplitude and shortening. Both agents inhibited MHC synthesis, but only verapamil accelerated MHC degradation. Thus MHC half-life does not change in parallel with contractile activity but rather more closely follows changes in [Ca2+]i. [Ca2+]i transients appear critical in maintaining myofibrillar assembly and preventing accelerated MHC proteolysis.

Regulation of rat ventricular myosin heavy chain expression by serum and contractile activity

1994 ◽  
Vol 267 (2) ◽  
pp. C520-C528 ◽  
Author(s):  
M. Qi ◽  
K. Ojamaa ◽  
E. G. Eleftheriades ◽  
I. Klein ◽  
A. M. Samarel
Keyword(s):  
Myosin Heavy Chain ◽  
Growth Medium ◽  
Heavy Chain ◽  
Ventricular Myocytes ◽  
Contractile Activity ◽  
Cellular Growth ◽  
Neonatal Rat ◽  
Mrna Levels ◽  
Serum Free ◽  
Serum Stimulation

To quantitatively analyze the effects of serum stimulation and contractile activity and their interaction on cellular growth and cardiac myosin heavy chain (MHC) gene expression, spontaneously contracting neonatal rat ventricular myocytes in primary culture were maintained in serum-free growth medium or growth medium supplemented with fetal bovine serum. Contractile activity in paired cultures was inhibited by addition of the calcium channel blocker verapamil (10 microM) to the culture medium. Both serum stimulation and contractile activity produced myocyte hypertrophy as assessed by increases in total protein, total RNA, protein-to-DNA ratios, and total MHC protein content. MHC isoenzyme analysis indicated that both MHC-alpha and MHC-beta proteins accumulated in response to serum stimulation and/or contractile activity. The increases in MHC-beta protein resulting from serum stimulation and contractile activity occurred in parallel with increases in MHC-beta mRNA. In contrast, MHC-alpha mRNA levels were relatively unaffected by serum stimulation but appeared to decrease in response to contractile activity. The protein kinase inhibitor staurosporine (5 nM) reduced MHC-beta expression in serum-free, contracting cultures and also prevented the serum-induced increase in MHC-beta mRNA observed in both contracting and arrested myocytes. Staurosporine also increased MHC-alpha mRNA levels in serum-free, contracting, and verapamil-arrested myocytes. These data suggest that both humoral and mechanical factors regulate MHC isoenzyme expression and cellular growth in neonatal ventricular myocytes.

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