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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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MR-1 is necessary for myomesin-1 translocation and SUMO-1-induced promotion of sarcomere organization. (a) Immunofluorescent staining of myomesin-1 showing translocation of myomesin-1 in neonatal rat cardiomyocytes. Myomesin-1 predominantly localized in the nucleus in primary cultured neonatal rat cardiomyocytes (control). With MR-1 transfected into cardiomyocytes for 24 h, myomesin-1 translocated to cytoplasm (MR-1). Transfection with pcDNA3.1 plasmid showed localization of myomesin-1 similar to the control (vector). On transfection with small ubiquitin-like modifier-1 (SUMO-1), myomesin-1 shifted to cytoplasm similar to with MR-1 transfection. Myomesin-1 was localized in the nuclear area with RNAi silencing (RNAi). Transfection with SUMO-1 in MR-1-silenced cardiomyocytes showed that myomesin-1 localized in nucleus and peri-nuclear area (SUMO-1+RNAi). (b) Silencing of MR-1 attenuated SUMO-1-induced promotion of sarcomere organization as detected by FITC-labeled phalloidin. Sarcomere organization with SUMO-1 transfected into cardiomyocytes for 16 h (SUMO-1) and with RNA interference silencing (SUMO-1+RNAi), *P<0.05. A full color version of this figure is available at the Hypertension Research journal online.
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fig4: MR-1 is necessary for myomesin-1 translocation and SUMO-1-induced promotion of sarcomere organization. (a) Immunofluorescent staining of myomesin-1 showing translocation of myomesin-1 in neonatal rat cardiomyocytes. Myomesin-1 predominantly localized in the nucleus in primary cultured neonatal rat cardiomyocytes (control). With MR-1 transfected into cardiomyocytes for 24 h, myomesin-1 translocated to cytoplasm (MR-1). Transfection with pcDNA3.1 plasmid showed localization of myomesin-1 similar to the control (vector). On transfection with small ubiquitin-like modifier-1 (SUMO-1), myomesin-1 shifted to cytoplasm similar to with MR-1 transfection. Myomesin-1 was localized in the nuclear area with RNAi silencing (RNAi). Transfection with SUMO-1 in MR-1-silenced cardiomyocytes showed that myomesin-1 localized in nucleus and peri-nuclear area (SUMO-1+RNAi). (b) Silencing of MR-1 attenuated SUMO-1-induced promotion of sarcomere organization as detected by FITC-labeled phalloidin. Sarcomere organization with SUMO-1 transfected into cardiomyocytes for 16 h (SUMO-1) and with RNA interference silencing (SUMO-1+RNAi), *P<0.05. A full color version of this figure is available at the Hypertension Research journal online.

Mentions: The exact mechanism of MR-1-promoted sarcomere organization was asked. Myomesin-1, which was thought to be a cytoskeletal protein, is also present in the nucleus of myocytes of newborn pups, resulting in differential regulation of several gene products. The shuttling of myomesin-1 suggests that myomesin-1 may have special roles in the differentiation of striated muscle in addition to regulating its contractile functions.11 Overexpression of MR-1 induces translocation of myomesin-1. Myomesin-1 is exclusively cytoplasmic in adult cardiomyocytes but was predominantly localized in the nucleus when expressed in primary cultured neonatal rat cardiomyocytes (Figure 4a—control). Transfection with vector did not affect the nuclear localization (Figure 4a—vector). Immunostaining revealed that in cardiomyocytes transfected with MR-1 for 24 h, myomesin-1 located in the nucleus shifted to the cytoplasm (Figure 4a—MR1), where it functions in myofibrillogenesis.


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

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

MR-1 is necessary for myomesin-1 translocation and SUMO-1-induced promotion of sarcomere organization. (a) Immunofluorescent staining of myomesin-1 showing translocation of myomesin-1 in neonatal rat cardiomyocytes. Myomesin-1 predominantly localized in the nucleus in primary cultured neonatal rat cardiomyocytes (control). With MR-1 transfected into cardiomyocytes for 24 h, myomesin-1 translocated to cytoplasm (MR-1). Transfection with pcDNA3.1 plasmid showed localization of myomesin-1 similar to the control (vector). On transfection with small ubiquitin-like modifier-1 (SUMO-1), myomesin-1 shifted to cytoplasm similar to with MR-1 transfection. Myomesin-1 was localized in the nuclear area with RNAi silencing (RNAi). Transfection with SUMO-1 in MR-1-silenced cardiomyocytes showed that myomesin-1 localized in nucleus and peri-nuclear area (SUMO-1+RNAi). (b) Silencing of MR-1 attenuated SUMO-1-induced promotion of sarcomere organization as detected by FITC-labeled phalloidin. Sarcomere organization with SUMO-1 transfected into cardiomyocytes for 16 h (SUMO-1) and with RNA interference silencing (SUMO-1+RNAi), *P<0.05. A full color version of this figure is available at the Hypertension Research journal online.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: MR-1 is necessary for myomesin-1 translocation and SUMO-1-induced promotion of sarcomere organization. (a) Immunofluorescent staining of myomesin-1 showing translocation of myomesin-1 in neonatal rat cardiomyocytes. Myomesin-1 predominantly localized in the nucleus in primary cultured neonatal rat cardiomyocytes (control). With MR-1 transfected into cardiomyocytes for 24 h, myomesin-1 translocated to cytoplasm (MR-1). Transfection with pcDNA3.1 plasmid showed localization of myomesin-1 similar to the control (vector). On transfection with small ubiquitin-like modifier-1 (SUMO-1), myomesin-1 shifted to cytoplasm similar to with MR-1 transfection. Myomesin-1 was localized in the nuclear area with RNAi silencing (RNAi). Transfection with SUMO-1 in MR-1-silenced cardiomyocytes showed that myomesin-1 localized in nucleus and peri-nuclear area (SUMO-1+RNAi). (b) Silencing of MR-1 attenuated SUMO-1-induced promotion of sarcomere organization as detected by FITC-labeled phalloidin. Sarcomere organization with SUMO-1 transfected into cardiomyocytes for 16 h (SUMO-1) and with RNA interference silencing (SUMO-1+RNAi), *P<0.05. A full color version of this figure is available at the Hypertension Research journal online.
Mentions: The exact mechanism of MR-1-promoted sarcomere organization was asked. Myomesin-1, which was thought to be a cytoskeletal protein, is also present in the nucleus of myocytes of newborn pups, resulting in differential regulation of several gene products. The shuttling of myomesin-1 suggests that myomesin-1 may have special roles in the differentiation of striated muscle in addition to regulating its contractile functions.11 Overexpression of MR-1 induces translocation of myomesin-1. Myomesin-1 is exclusively cytoplasmic in adult cardiomyocytes but was predominantly localized in the nucleus when expressed in primary cultured neonatal rat cardiomyocytes (Figure 4a—control). Transfection with vector did not affect the nuclear localization (Figure 4a—vector). Immunostaining revealed that in cardiomyocytes transfected with MR-1 for 24 h, myomesin-1 located in the nucleus shifted to the cytoplasm (Figure 4a—MR1), where it functions in myofibrillogenesis.

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