Homogenous protein programming in the mammalian left and right ventricle free walls

Phillips, Darci; Aponte, Angel; Covián, Raúl; Neufeld, Edward B.; Yu, Zu‐Xi; Balaban, Robert S.

doi:10.1152/physiolgenomics.00121.2011

Cited by 32 publications

(35 citation statements)

References 33 publications

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“…Application of this technology revealed that the left and right ventricle of the mouse has negligible differences in their coreproteome. While this manuscript was in press, a comparative proteome study of the left and right ventricle of the rabbit heart revealed similar results (31).…”

Section: Discussionsupporting

confidence: 53%

In-depth Quantitative Cardiac Proteomics Combining Electron Transfer Dissociation and the Metalloendopeptidase Lys-N with the SILAC Mouse

Scholten

Mohammed

Low

et al. 2011

Molecular & Cellular Proteomics

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In quantitative proteomics stable isotope labeling has progressed from cultured cells toward the total incorporation of labeled atoms or amino acids into whole multicellular organisms. For instance, the recently introduced 13 C 6 -lysine labeled SILAC mouse allows accurate comparison of protein expression directly in tissue. In this model, only lysine, but not arginine, residues are isotope labeled, as the latter may cause complications to the quantification by in vivo conversion of arginine to proline. The sole labeling of lysines discourages the use of trypsin, as not all peptides will be quantifiable. Therefore, in the initial work Lys-C was used for digestion. Here, we demonstrate that the lysine-directed protease metalloendopeptidase Lys-N is an excellent alternative. As lysine directed peptides generally yield longer and higher charged peptides, alongside the more traditional collision induced dissociation we also implemented electron transfer dissociation in a quantitative stable isotope labeling with amino acid in cell culture workflow for the first time. The utility of these two complementary approaches is highlighted by investigating the differences in protein expression between the left and right ventricle of a mouse heart. Using Lys-N and electron transfer dissociation yielded coverage to a depth of 3749 proteins, which is similar as earlier investigations into the murine heart proteome. In addition, this strategy yields quantitative information on ϳ2000 proteins with a median coverage of four peptides per protein in a single strong cation exchange-liquid chromatography-MS experiment, revealing that the left and right ventricle proteomes are very similar qualitatively as well as quantitatively. Molecular & Cellular Proteomics

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Section: Discussionsupporting

confidence: 53%

In-depth Quantitative Cardiac Proteomics Combining Electron Transfer Dissociation and the Metalloendopeptidase Lys-N with the SILAC Mouse

Scholten

Mohammed

Low

et al. 2011

Molecular & Cellular Proteomics

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“…The data of Hyder et al (5) suggest that brain P s and ΣP ns are also fixed across wide ranges of neuronal activity within a species brain and, if properly normalized, also apply across a wide range of brain sizes and cognitive abilities. A linear relationship between neuronal activity and energy metabolism using 13 C NMR estimates of neurotransmitter cycling and oxidative ATP production (7,8) has also been observed, consistent with fixed values of brain P s and ΣP ns . Taken together, these results suggest that the efficiency of the cellular mechanisms empowering brain-signaling activity by aerobic metabolism are very similar over a wide range of activity and between species.…”

supporting

confidence: 62%

“…Thus, in the liver the metabolic capacity per cell increases with decreasing animal size. In contrast, the cardiac [COX] and PVM remains constant with the heart size (10) and chamber (13), indicating that the metabolic capacity per cell of heart muscle remains essentially constant. What is the effect of brain size on neuronal PVM?…”

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confidence: 99%

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Allometry of brain metabolism

Balaban

2013

Proc. Natl. Acad. Sci. U.S.A.

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Allometry refers to biological scaling relationships (1). With regard to metabolic rate, the earliest allometric studies demonstrated a complex inverse relationship between body size and resting metabolic rate (2-4). Subsequent studies have focused, without much success, on describing the cellular mechanisms of this relationship. The energy requirements of the cell can be crudely divided into two areas: differentiated external work, such as muscle contraction, neuron firing, transepithelial transport, and the basic cellular homeostasis processes, such as maintaining the cellular milieu, temperature, and so forth, which all cells have in common. In the literature-based analysis by Hyder et al. (5) in PNAS, metabolic and functional data from the rat and human brain were evaluated in a top-down analysis of two phenomenological coefficients (P s and P ns ) that correspond to these energy sinks. P s has units of ATP used per neuron per spike and represents the energy efficiency of neuron signaling. P nsA and P nsN have units of ATP used per neuron per second in astrocytes and neurons, respectively, and represent the energy efficiency to maintain cellular homeostasis, (i.e., steady-state ion gradients, temperature, and so forth). The total ATPase activity (E tot ) in ATP used per second per square centimeter was reduced to: E tot = P s × (neuron firing rate) + ΣP ns × (specific cell density). What Hyder et al. determined in this study is whether the coefficients P s and ΣP ns were constants as a function of functional state and size of the brain. Rat brain ΣP ns and P s were initially evaluated because more measures have become available. The pentobarbital state, with no signaling activity, was used to determine ΣP ns . The relative contribution of P nsA and P nsN to ΣP ns was determined for comparison with humans. The pentobarbital state ATPase activity was assumed to be the plasma membrane ionic leak inversely proportional to cellular membrane resistance; this is likely one of the weakest estimates of the study because plasma membrane potential and many other energy-requiring processes might be differentially weighted in these cell types. In addition, species differences in other cell-type volumes, such as glial cells, could also be problematic. However, the ΣP ns estimate for the rat is reasonable using the pentobarbital condition and supported by a similar estimate of ΣP ns by fitting the varying neuronal activity data without phenobarbital. P s was determined from linear leastsquares analysis of the measured glucose consumption in the brain under a variety of activity conditions. A linear relationship between the calculated glucose consumption rate with the measured rate was obtained with a constant P s of 4.8 × 10 9 ATP per spike per neuron and ΣP ns 1.6 × 10 9 ATP per neuron per second. This excellent linear fit is consistent with the notion that the energetic transfer functions P s and ΣP ns are constant in the rat over a wide range of activities.Because of the lack of comparable neuronal activity in the human...

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“…Phillips et al (29) have shown that overall protein expression levels in the normal, nondiseased rabbit LV and RV are similar. These authors suggested that the lower metabolic stress of the RV would approach that of the LV at maximal workloads and that the identical protein levels associated with energy conversion and function in the LV and RV would therefore be differentially stressed at maximal workloads.…”

Section: H704mentioning

confidence: 98%

Pressure-overload hypertrophy of the developing heart reveals activation of divergent gene and protein pathways in the left and right ventricular myocardium

Friehs

Cowan

Choi

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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and left ventricular (LV) myocardium differ in their pathophysiological response to pressure-overload hypertrophy. In this report we use microarray and proteomic analyses to identify pathways modulated by LV-aortic banding (AOB) and RV-pulmonary artery banding (PAB) in the immature heart. Newborn New Zealand White rabbits underwent banding of the descending thoracic aorta [LV-AOB; n ϭ 6]. RV-PAB was achieved by banding the pulmonary artery (n ϭ 6). Controls (n ϭ 6 each) were sham-manipulated. After 4 (LV-AOB) and 6 (RV-PAB) wk recovery, the hearts were removed and matched RNA and proteins samples were isolated for microarray and proteomic analysis. Microarray and proteomic data demonstrate that in LV-AOB there is increased transcript expression levels for oxidative phosphorylation, mitochondria energy pathways, actin, ILK, hypoxia, calcium, and protein kinase-A signaling and increased protein expression levels of proteins for cellular macromolecular complex assembly and oxidative phosphorylation. In RV-PAB there is also an increased transcript expression levels for cardiac oxidative phosphorylation but increased protein expression levels for structural constituents of muscle, cardiac muscle tissue development, and calcium handling. These results identify divergent transcript and protein expression profiles in LV-AOB and RV-PAB and provide new insight into the biological basis of ventricular specific hypertrophy. The identification of these pathways should allow for the development of specific therapeutic interventions for targeted treatment and amelioration of LV-AOB and RV-PAB to ameliorate morbidity and mortality.heart; hypertrophy; microarray; proteomics VENTRICULAR OUTFLOW TRACT obstruction in congenital heart defects such as interrupted aortic arch, coarctation of the aorta on the left side, and pulmonary artery stenosis on the right side, causes progressive cardiac hypertrophy and, if unrelieved, leads to ventricular dilatation with contractile dysfunction and ultimately irreversible heart failure. Initially, the myocardium compensates to elevated pressure-loading by increasing wall thickness to normalize wall stress. These changes allow for maintenance of contractile function in left ventricular pressureoverload hypertrophy [LV-aortic banding (AOB)], whereas in right ventricular pressure-overload hypertrophy [RV-pulmonary artery banding (PAB)] these changes are less effective and progression to failure occurs more rapidly (2, 4, 15).Our previous studies using the rabbit model of LV-AOB and RV-PAB have demonstrated that disease progression involves both cellular and extracellular components of the myocardium. We have demonstrated that changes in cardiomyocyte viability, lack of adaptive capillary growth, fibrosis, and response to metabolic stress are differentially regulated in LV-AOB and RV-PAB (11,13,16,20). However, the mechanisms involved in the compensated phase of LV-AOB and RV-PAB have yet to be clearly elucidated. In this report we present microarray and proteomic analyses of the LV and RV during t...

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Homogenous protein programming in the mammalian left and right ventricle free walls

Cited by 32 publications

References 33 publications

In-depth Quantitative Cardiac Proteomics Combining Electron Transfer Dissociation and the Metalloendopeptidase Lys-N with the SILAC Mouse

In-depth Quantitative Cardiac Proteomics Combining Electron Transfer Dissociation and the Metalloendopeptidase Lys-N with the SILAC Mouse

Allometry of brain metabolism

Pressure-overload hypertrophy of the developing heart reveals activation of divergent gene and protein pathways in the left and right ventricular myocardium

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