Homogenous protein programming in the mammalian left and right ventricle free walls.
ABSTRACT Despite identical cardiac outputs, the right (RV) and left ventricle (LV) have very different embryological origins and resting workload. These differences suggest that the ventricles have different protein programming with regard to energy metabolism and contractile elements. The objective of this study was to determine the relative RV and LV protein expression levels, with an emphasis on energy metabolism. The RV and LV protein contents of the rabbit and porcine heart were determined with quantitative gel electrophoresis (2D-DIGE), mass spectrometry, and optical spectroscopy techniques. Surprisingly, the expression levels for more than 600 RV and LV proteins detected were similar. This included proteins many different compartments and metabolic pathways. In addition, no isoelectric shifts were detected in 2D-DIGE consistent with no differential posttranslational modifications in these proteins. Analysis of the RV and LV metabolic response to work revealed that the metabolic rate increases much faster with workload in the RV compared with LV. This implies that the generally lower metabolic stress of the RV actually approaches LV metabolic stress at maximum workloads. Thus, identical levels of energy conversion and mechanical elements in the RV and LV may be driven by the performance requirements at maximum workloads. In summary, the ventricles of the heart manage the differences in overall workload by modifying the amounts of cytosol, not its composition. The constant myocyte composition in the LV and RV implies that the ratio of energy metabolism and contractile elements may be optimal for the sustained cardiac contractile activity in the mammalian heart.
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ABSTRACT: The concentration of mitochondrial oxidative phosphorylation complexes (MOPCs) is tuned to the maximum energy conversion requirements of a given tissue; however, whether the activity of MOPCs is altered in response to acute changes in energy conversion demand is unclear. We hypothesized that MOPCs activity is modulated by tissue metabolic stress to maintain the energy-metabolism homeostasis. Metabolic stress was defined as the observed energy conversion rate/maximum energy conversion rate. The maximum energy conversion rate was assumed to be proportional to the concentration of MOPCs, as determined with optical spectroscopy, gel electrophoresis, and mass spectrometry. The resting metabolic stress of the heart and liver across the range of resting metabolic rates within an allometric series (mouse, rabbit, and pig) was determined from MPOCs content and literature respiratory values. The metabolic stress of the liver was high and nearly constant across the allometric series due to the proportional increase in MOPCs content with resting metabolic rate. In contrast, the MOPCs content of the heart was essentially constant in the allometric series, resulting in an increasing metabolic stress with decreasing animal size. The MOPCs activity was determined in native gels, with an emphasis on Complex V. Extracted MOPCs enzyme activity was proportional to resting metabolic stress across tissues and species. Complex V activity was also shown to be acutely modulated by changes in metabolic stress in the heart, in vivo and in vitro. The modulation of extracted MOPCs activity suggests that persistent posttranslational modifications (PTMs) alter MOPCs activity both chronically and acutely, specifically in the heart. Protein phosphorylation of Complex V was correlated with activity inhibition under several conditions, suggesting that protein phosphorylation may contribute to activity modulation with energy metabolic stress. These data are consistent with the notion that metabolic stress modulates MOPCs activity in the heart.AJP Regulatory Integrative and Comparative Physiology 02/2012; 302(9):R1034-48. DOI:10.1152/ajpregu.00596.2011 · 3.53 Impact Factor
- The Journal of General Physiology 06/2012; 139(6):407-14. DOI:10.1085/jgp.201210783 · 4.57 Impact Factor
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ABSTRACT: Right ventricular (RV) and left ventricular (LV) myocardium differ in their pathophysiological response to pressure-overload hypertrophy (POH). In this report we use microarray and proteomic analyses to identify pathways modulated by LV-, and RV-PAB in the immature heart. Newborn New Zealand White rabbits underwent banding of the descending thoracic aorta (LV-AOB; n=6). RV-PAB was achieved by banding the pulmonary artery (n=6). Controls (SC; n=6 each) were sham-manipulated. Following 4 (LV-AOB) and 6 weeks (RV-PAB) 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 signalling and increased protein expression levels of proteins for cellular macromolecular complex assembly and oxidative phosphorylation. In RV-PAB there is also and 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.AJP Heart and Circulatory Physiology 12/2012; 304(5). DOI:10.1152/ajpheart.00802.2012 · 4.01 Impact Factor