Cardiac hypertrophy: A matter of translation

Hannan, Ross D.; Jenkins, AK; Brandenburger, Yves

doi:10.1046/j.1440-1681.2003.03873.x

Cited by 141 publications

(132 citation statements)

References 102 publications

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“…Similar to the RNA data and in accordance with previous reports, 18 total LV protein content was significantly (PϽ0.01) higher (1.2-fold on average) in TAC, compared with sham, LV ( Figure 6A). To compare protein expression in sham and TAC LV and in sham and TAC EPI and ENDO LV samples, therefore, protein loading on SDS-PAGE gels was normalized to reflect the LVM/BW.…”

Section: Molecular Basis Of K ؉ Current Remodeling In Tac LVsupporting

confidence: 92%

“…3,4 In the molecular/biochemical analyses completed here, however, no significant changes in the expression levels of the I to,f (Kv4.2, Kv4.3, KChIP2) or I K1 (Kir2.1, Kir2.2) channel subunits in TAC (EPI and/or ENDO) LV were observed, consistent with the observed similarities in I to,f and I K1 amplitudes in TAC EPI and ENDO LV myocytes. As previously demonstrated, 18 the hypertrophic growth of cardiomyocytes with LVH is characterized by an increase in cell size without significant changes in cell number. In agreement with these previous reports, 18 TACinduced LVH was associated with global increases in LV RNA and protein expression.…”

Section: Molecular Remodeling Of K ؉ Channels In Tac-induced Lvhsupporting

confidence: 58%

“…As previously demonstrated, 18 the hypertrophic growth of cardiomyocytes with LVH is characterized by an increase in cell size without significant changes in cell number. In agreement with these previous reports, 18 TACinduced LVH was associated with global increases in LV RNA and protein expression. Because cardiomyocytes contribute more than 90% to the total mass of the myocardium, 1 the increase in LVM, as well as in RNA and protein content, with LVH predominantly reflects cardiomyocyte enlargement.…”

Section: Molecular Remodeling Of K ؉ Channels In Tac-induced Lvhsupporting

confidence: 58%

“…17 Data were analyzed using the threshold cycle relative quantification method, with hypoxanthine guanine phosphoribosyl transferase (HPRT) as the endogenous control. Because hypertrophy is associated with a generalized increase in transcript and protein content without an increase in cell numbers, 18 transcript expression data determined in each sham and TAC (LV, EPI and ENDO) sample were multiplied by the LV mass to body weight ratio (LVM/BW) determined in the same animal.…”

Section: Quantitative Rt-pcrmentioning

confidence: 99%

“…This observation is consistent with previous findings demonstrating that RNA synthesis/content in the LV is increased with hypertrophy, reflecting increased myocyte size, without an increase in myocyte number. 18 Transcript expression levels determined by quantitative RT-PCR on sham and TAC LV, and on EPI and ENDO LV, samples were, therefore, normalized to the LVM/BW determined in each animal. Consistent with the increase in total RNA, expression of several endogenous control genes (18S RNA, GAPDH, HPRT, RNA polymerase II [RNA Pol II]) 17 was increased in TAC, compared with sham, LV ( Figure 5B).…”

Section: Molecular Basis Of K ؉ Current Remodeling In Tac LVmentioning

confidence: 99%

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Left Ventricular Hypertrophy

Ebert¹

2005

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Abstract-Left ventricular hypertrophy (LVH) is associated with electric remodeling and increased arrhythmia risk, although the underlying mechanisms are poorly understood. In the experiments here, functional voltage-gated (Kv) and inwardly rectifying (Kir) K ϩ channel remodeling was examined in a mouse model of pressure overload-induced LVH, produced by transverse aortic constriction (TAC). Action potential durations (APDs) at 90% repolarization in TAC LV myocytes and QT c intervals in TAC mice were prolonged. Mean whole-cell membrane capacitance (C m ) was higher, and Key Words: hypertrophy Ⅲ arrhythmia Ⅲ heart failure L eft ventricular hypertrophy (LVH) is an adaptive response of the myocardium to an increase in load. 1 LVH is seen in various disease states including hypertension and myocardial infarction, as well as in valvular and congenital heart diseases. 1 LVH is also observed in physiological states following rigorous, prolonged exercise. 2 Although physiological LVH does not confer increased morbidity and mortality, pathological LVH is consistently associated with prolongation of ventricular action potentials and alterations in the dispersion of repolarization, both of which result in electric instability and increase the propensity to develop lifethreatening arrhythmias. 3 Several lines of evidence suggest that these electric changes reflect, at least in part, alterations in the functioning of the K ϩ channels that underlie ventricular action potential repolarization. 3,4 Various experimental models of LVH, 5-7 including pressure overload-induced LVH, 8,9 have been developed to explore the mechanisms underlying K ϩ current remodeling.Although several studies have examined regional differences in remodeling, 8 -11 few have probed the underlying molecular and cellular mechanisms. In the studies here, a mouse model of pressure overload-induced LVH, produced by transverse aortic constriction (TAC), was exploited to quantify the effects of LVH on repolarizing K ϩ currents in LV myocytes and to delineate the mechanisms underlying K ϩ current remodeling. These experiments revealed that APDs were prolonged in TAC LV myocytes and that QT c intervals were increased in TAC mice. Mean whole-cell membrane capacitance (C m ) was increased significantly, and the densities of voltage-gated K ϩ (Kv) and inwardly rectifying K ϩ (Kir) currents were reduced in TAC LV myocytes. Further electrophysiological, molecular, and biochemical analyses revealed marked regional differences in the effects of LVH and that distinct cellular and molecular mechanisms contribute to the functional remodeling of repolarizing Kv and Kir currents.

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Section: Molecular Basis Of K ؉ Current Remodeling In Tac LVsupporting

confidence: 92%

Section: Molecular Remodeling Of K ؉ Channels In Tac-induced Lvhsupporting

confidence: 58%

Section: Molecular Remodeling Of K ؉ Channels In Tac-induced Lvhsupporting

confidence: 58%

Section: Quantitative Rt-pcrmentioning

confidence: 99%

Section: Molecular Basis Of K ؉ Current Remodeling In Tac LVmentioning

confidence: 99%

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Left Ventricular Hypertrophy

Ebert¹

2005

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Signaling to the ribosome in cancer—It is more than just mTORC1

et al. 2011

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SummaryIt is becoming increasingly clear that dysregulation of protein synthesis contributes to a range of diseases characterized by tissue overgrowth. These include arterial stenosis, cardiac hypertrophy, hamartomas, and cancer. The central hub for the regulation of protein synthesis is the ribosome, where the key signaling pathways downstream of RAS, MYC, and phosphatidylinositol-3-kinase (PI3K) converge to confer exquisite, coordinated control of ribosome synthesis and function. Such cooperation ensures strict regulation of protein synthesis rates and cell growth. This review will focus on the role the PI3K/AKT/mammalian target of rapamycin complex 1 (mTORC1) pathway plays in regulating ribosome function during both health and disease, its interaction with the other key growth regulatory pathways activated by RAS and MYC, and the therapeutic potential for targeting this network.

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Endothelin‐1‐ and isoproterenol‐induced differential protein expression and signaling pathway in HL‐1 cardiomyocytes

Hong

Song

et al. 2010

Proteomics

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It is well known that the two chemical compounds endothelin-1 (ET-1) and isoproterenol (ISO) can individually induce cardiac hypertrophy through G protein-coupled receptors in cardiomyocytes. However, the cardiac hypertrophy signaling pathway activated by ET-1 and ISO is not well defined. Therefore, we investigated the protein expression profile and signaling transduction in HL-l cardiomyocyte cells treated with ET-1 and ISO. Following separation of the cell lysates by using 2-DE and silver staining, we identified 16 protein spots that were differentially expressed as compared to the controls. Of these 16 spots, three changed only after treatment with ET-1, whereas four changed only after treatment with ISO, suggesting that these two stimuli could induce different signaling pathways. In order to reveal the differences between ET-1- and ISO-induced signaling, we studied the different events that occur at each step of the signaling pathways, when selected biocomponents were blocked by inhibitors. Our results indicated that ET-1 and ISO used different pathways for phosphorylation of glycogen synthase kinase-3β (GSK3β). ET-1 mainly used the mitogen-activated protein kinase and phosphatidylinositol-3-kinase/AKT pathways to activate GSK3β, whereas under ISO stimulation, only the phosphatidylinositol-3-kinase/AKT pathway was required to trigger the GSK3β pathway. Furthermore, the strength of the GSK3β signal in ISO-induced cardiac hypertrophy was stronger than that in ET-1-induced cardiac hypertrophy. We found that these two agonists brought about different changes in the protein expression of HL-1 cardiomyocytes through distinct signaling pathways even though the destination of the two signaling pathways was the same.

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Cardiac hypertrophy: A matter of translation

Cited by 141 publications

References 102 publications

Left Ventricular Hypertrophy

Left Ventricular Hypertrophy

Signaling to the ribosome in cancer—It is more than just mTORC1

Endothelin‐1‐ and isoproterenol‐induced differential protein expression and signaling pathway in HL‐1 cardiomyocytes

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