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Myofibrillogenesis regulator 1 induces hypertrophy by promoting sarcomere organization in neonatal rat cardiomyocytes.

Wang X, Liu X, Wang S, Luan K - Hypertens. Res. (2012)

Bottom Line: Hypertrophic hallmarks such as cell size and [(3)H]-leucine incorporation were significantly increased when MR-1 was transfected into cardiomyocytes for 48 h.Transfection with small ubiquitin-like modifier-1 (SUMO-1) mimicked the effect of MR-1 inducing translocation of myomesin-1.However, transfection with SUMO-1 in MR-1-silenced cardiomyocytes failed to induce translocation and sarcomere organization, even though SUMO-1 expression was at the same level.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, PLA General Hospital, Beijing, China.

ABSTRACT
Human myofibrillogenesis regulator 1, a novel 17-kDa protein, is closely involved in cardiac hypertrophy. We studied the molecular mechanism that links MR-1 to hypertrophic response. Hypertrophic hallmarks such as cell size and [(3)H]-leucine incorporation were significantly increased when MR-1 was transfected into cardiomyocytes for 48 h. However, sarcomere organization was promoted when MR-1 was transfected for 8 h. The finding that cardiac hypertrophy was induced long after increase of sarcomere organization indicates that the promoted sarcomere organization may be one of the crucial factors causing hypertrophy. Furthermore, when MR-1 was transfected into cardiomyocytes, the nuclear localization of myomesin-1 was shifted to the cytoplasm. Transfection with small ubiquitin-like modifier-1 (SUMO-1) mimicked the effect of MR-1 inducing translocation of myomesin-1. However, transfection with SUMO-1 in MR-1-silenced cardiomyocytes failed to induce translocation and sarcomere organization, even though SUMO-1 expression was at the same level. Overexpression of MR-1 may induce cardiomyocyte hypertrophy via myomesin-1-mediated sarcomere organization.

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The relative amounts of MR-1 expression levels and assessment of hypertrophic hallmarks in cardiomyocytes transfected with MR-1. (a) MR-1 was overexpressed in neonatal rat ventricular cardiomyocytes at 16–48 h when transfected with pcDNA3.1-hMR1 plasmid (MR-1) compared with the culture transfected with pcDNA3.1 (vector). *P<0.05 vs. vector. (b) mRNA levels of atrial natriuretic factor (ANF) and brain natriuretic protein (BNP) normalized to that of glyceraldehyde phosphate dehydrogenase (GAPDH) after 24-h transfection with MR-1. (c) Incorporation of [3H]-Leucine reflecting the velocity of protein synthesis after up to 48-h transfection with MR-1. *P<0.05 vs. vector. (d) Mean area of cell surface with MR-1 transfected for 24 and 48 h.
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fig1: The relative amounts of MR-1 expression levels and assessment of hypertrophic hallmarks in cardiomyocytes transfected with MR-1. (a) MR-1 was overexpressed in neonatal rat ventricular cardiomyocytes at 16–48 h when transfected with pcDNA3.1-hMR1 plasmid (MR-1) compared with the culture transfected with pcDNA3.1 (vector). *P<0.05 vs. vector. (b) mRNA levels of atrial natriuretic factor (ANF) and brain natriuretic protein (BNP) normalized to that of glyceraldehyde phosphate dehydrogenase (GAPDH) after 24-h transfection with MR-1. (c) Incorporation of [3H]-Leucine reflecting the velocity of protein synthesis after up to 48-h transfection with MR-1. *P<0.05 vs. vector. (d) Mean area of cell surface with MR-1 transfected for 24 and 48 h.

Mentions: We first examined the effect of the MR-1-overexpression model and found successful overexpression of MR-1 in MR-1-transfected cardiomyocytes, with an increase in expression by 1.6-fold at 8 h, 2.8-fold at 16 h, 3.4-fold at 24 h and 3.4-fold at 48 h as compared with pcDNA3.1 (vector)-transfected cultures (Figure 1a, *P<0.05). In determining hypertrophy, three hypertrophic hallmarks, that is, [3H]-leucine incorporation, mean area of cell surface and expression levels of ANF and BNP, were used. Compared with the vector control with MR-1 transfection for 24 h, ANF and BNP mRNA expression was increased by 1.1- and 0.9-fold, respectively (P<0.05) (Figure 1b). At 48 h of transfection, protein-synthesis velocity, as determined by [3H]-Leucine incorporation, was increased 0.9-fold (3333.5±106.1 vs. 1789.3±83.0 ccpm; P<0.05) (Figure 1c) and cell size was significantly increased by 1.0-fold that of the vector control (18 487.9±3804.9 vs. 8998.2±1427.7 μm2, P<0.05) (Figure 1d).


Myofibrillogenesis regulator 1 induces hypertrophy by promoting sarcomere organization in neonatal rat cardiomyocytes.

Wang X, Liu X, Wang S, Luan K - Hypertens. Res. (2012)

The relative amounts of MR-1 expression levels and assessment of hypertrophic hallmarks in cardiomyocytes transfected with MR-1. (a) MR-1 was overexpressed in neonatal rat ventricular cardiomyocytes at 16–48 h when transfected with pcDNA3.1-hMR1 plasmid (MR-1) compared with the culture transfected with pcDNA3.1 (vector). *P<0.05 vs. vector. (b) mRNA levels of atrial natriuretic factor (ANF) and brain natriuretic protein (BNP) normalized to that of glyceraldehyde phosphate dehydrogenase (GAPDH) after 24-h transfection with MR-1. (c) Incorporation of [3H]-Leucine reflecting the velocity of protein synthesis after up to 48-h transfection with MR-1. *P<0.05 vs. vector. (d) Mean area of cell surface with MR-1 transfected for 24 and 48 h.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368235&req=5

fig1: The relative amounts of MR-1 expression levels and assessment of hypertrophic hallmarks in cardiomyocytes transfected with MR-1. (a) MR-1 was overexpressed in neonatal rat ventricular cardiomyocytes at 16–48 h when transfected with pcDNA3.1-hMR1 plasmid (MR-1) compared with the culture transfected with pcDNA3.1 (vector). *P<0.05 vs. vector. (b) mRNA levels of atrial natriuretic factor (ANF) and brain natriuretic protein (BNP) normalized to that of glyceraldehyde phosphate dehydrogenase (GAPDH) after 24-h transfection with MR-1. (c) Incorporation of [3H]-Leucine reflecting the velocity of protein synthesis after up to 48-h transfection with MR-1. *P<0.05 vs. vector. (d) Mean area of cell surface with MR-1 transfected for 24 and 48 h.
Mentions: We first examined the effect of the MR-1-overexpression model and found successful overexpression of MR-1 in MR-1-transfected cardiomyocytes, with an increase in expression by 1.6-fold at 8 h, 2.8-fold at 16 h, 3.4-fold at 24 h and 3.4-fold at 48 h as compared with pcDNA3.1 (vector)-transfected cultures (Figure 1a, *P<0.05). In determining hypertrophy, three hypertrophic hallmarks, that is, [3H]-leucine incorporation, mean area of cell surface and expression levels of ANF and BNP, were used. Compared with the vector control with MR-1 transfection for 24 h, ANF and BNP mRNA expression was increased by 1.1- and 0.9-fold, respectively (P<0.05) (Figure 1b). At 48 h of transfection, protein-synthesis velocity, as determined by [3H]-Leucine incorporation, was increased 0.9-fold (3333.5±106.1 vs. 1789.3±83.0 ccpm; P<0.05) (Figure 1c) and cell size was significantly increased by 1.0-fold that of the vector control (18 487.9±3804.9 vs. 8998.2±1427.7 μm2, P<0.05) (Figure 1d).

Bottom Line: Hypertrophic hallmarks such as cell size and [(3)H]-leucine incorporation were significantly increased when MR-1 was transfected into cardiomyocytes for 48 h.Transfection with small ubiquitin-like modifier-1 (SUMO-1) mimicked the effect of MR-1 inducing translocation of myomesin-1.However, transfection with SUMO-1 in MR-1-silenced cardiomyocytes failed to induce translocation and sarcomere organization, even though SUMO-1 expression was at the same level.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathophysiology, PLA General Hospital, Beijing, China.

ABSTRACT
Human myofibrillogenesis regulator 1, a novel 17-kDa protein, is closely involved in cardiac hypertrophy. We studied the molecular mechanism that links MR-1 to hypertrophic response. Hypertrophic hallmarks such as cell size and [(3)H]-leucine incorporation were significantly increased when MR-1 was transfected into cardiomyocytes for 48 h. However, sarcomere organization was promoted when MR-1 was transfected for 8 h. The finding that cardiac hypertrophy was induced long after increase of sarcomere organization indicates that the promoted sarcomere organization may be one of the crucial factors causing hypertrophy. Furthermore, when MR-1 was transfected into cardiomyocytes, the nuclear localization of myomesin-1 was shifted to the cytoplasm. Transfection with small ubiquitin-like modifier-1 (SUMO-1) mimicked the effect of MR-1 inducing translocation of myomesin-1. However, transfection with SUMO-1 in MR-1-silenced cardiomyocytes failed to induce translocation and sarcomere organization, even though SUMO-1 expression was at the same level. Overexpression of MR-1 may induce cardiomyocyte hypertrophy via myomesin-1-mediated sarcomere organization.

Show MeSH
Related in: MedlinePlus