PMID- 19498199
OWN - NLM
STAT- MEDLINE
DCOM- 20090803
LR  - 20211020
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Print)
IS  - 0009-7330 (Linking)
VI  - 105
IP  - 1
DP  - 2009 Jul 2
TI  - Cardiac muscle ring finger-1 increases susceptibility to heart failure in vivo.
PG  - 80-8
LID - 10.1161/CIRCRESAHA.109.194928 [doi]
AB  - Muscle ring finger (MuRF)1 is a muscle-specific protein implicated in the 
      regulation of cardiac myocyte size and contractility. MuRF2, a closely related 
      family member, redundantly interacts with protein substrates and heterodimerizes 
      with MuRF1. Mice lacking either MuRF1 or MuRF2 are phenotypically normal, whereas 
      mice lacking both proteins develop a spontaneous cardiac and skeletal muscle 
      hypertrophy, indicating cooperative control of muscle mass by MuRF1 and MuRF2. To 
      identify the unique role that MuRF1 plays in regulating cardiac hypertrophy in 
      vivo, we created transgenic mice expressing increased amounts of cardiac MuRF1. 
      Adult MuRF1 transgenic (Tg(+)) hearts exhibited a nonprogressive thinning of the 
      left ventricular wall and a concomitant decrease in cardiac function. 
      Experimental induction of cardiac hypertrophy by transaortic constriction (TAC) 
      induced rapid failure of MuRF1 Tg(+) hearts. Microarray analysis identified that 
      the levels of genes associated with metabolism (and in particular mitochondrial 
      processes) were significantly altered in MuRF1 Tg(+) hearts, both at baseline and 
      during the development of cardiac hypertrophy. Surprisingly, ATP levels in MuRF1 
      Tg(+) mice did not differ from wild-type mice despite the depressed contractility 
      following TAC. In comparing the level and activity of creatine kinase (CK) 
      between wild-type and MuRF1 Tg(+) hearts, we found that mCK and CK-M/B protein 
      levels were unaffected in MuRF1 Tg(+) hearts; however, total CK activity was 
      significantly inhibited. We conclude that increased expression of cardiac MuRF1 
      results in a broad disruption of primary metabolic functions, including 
      alterations in CK activity that leads to increased susceptibility to heart 
      failure following TAC. This study demonstrates for the first time a role for 
      MuRF1 in the regulation of cardiac energetics in vivo.
FAU - Willis, Monte S
AU  - Willis MS
AD  - Carolina Cardiovascular Biology Center, University of North Carolina, Chapel 
      Hill, 27599-7525, USA. monte_willis@med.unc.edu
FAU - Schisler, Jonathan C
AU  - Schisler JC
FAU - Li, Luge
AU  - Li L
FAU - Rodriguez, Jessica E
AU  - Rodriguez JE
FAU - Hilliard, Eleanor G
AU  - Hilliard EG
FAU - Charles, Peter C
AU  - Charles PC
FAU - Patterson, Cam
AU  - Patterson C
LA  - eng
GR  - R01HL065619/HL/NHLBI NIH HHS/United States
GR  - R01 HL065619-08/HL/NHLBI NIH HHS/United States
GR  - R01 HL065619-07/HL/NHLBI NIH HHS/United States
GR  - R01 HL065619-09/HL/NHLBI NIH HHS/United States
GR  - T32 HL083828/HL/NHLBI NIH HHS/United States
GR  - R01 HL065619/HL/NHLBI NIH HHS/United States
GR  - R01 HL104129/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090604
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - 0 (Muscle Proteins)
RN  - 0 (Tripartite Motif Proteins)
RN  - EC 2.3.2.27 (Trim63 protein, mouse)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.3.2 (Creatine Kinase)
SB  - IM
MH  - Animals
MH  - Cardiomegaly/genetics
MH  - Creatine Kinase/metabolism
MH  - Disease Susceptibility
MH  - Gene Expression Profiling
MH  - Heart Failure/*etiology/genetics
MH  - Metabolism/genetics
MH  - Mice
MH  - Mice, Transgenic
MH  - Muscle Proteins/genetics/*physiology
MH  - Tripartite Motif Proteins
MH  - Ubiquitin-Protein Ligases/genetics/*physiology
PMC - PMC2737442
MID - NIHMS127242
COIS- Disclosures: None.
EDAT- 2009/06/06 09:00
MHDA- 2009/08/04 09:00
PMCR- 2010/07/02
CRDT- 2009/06/06 09:00
PHST- 2009/06/06 09:00 [entrez]
PHST- 2009/06/06 09:00 [pubmed]
PHST- 2009/08/04 09:00 [medline]
PHST- 2010/07/02 00:00 [pmc-release]
AID - CIRCRESAHA.109.194928 [pii]
AID - 10.1161/CIRCRESAHA.109.194928 [doi]
PST - ppublish
SO  - Circ Res. 2009 Jul 2;105(1):80-8. doi: 10.1161/CIRCRESAHA.109.194928. Epub 2009 
      Jun 4.