Congenital cardiomyopathy and pulmonary hypertension: Another fatal variant of cytochrome‐<i>c</i> oxidase deficiency

Venditti, Charles P.; Harris, Mary C.; Huff, Dale S.; Peterside, Iyalla; Munson, David; Weber, Howard S.; Rome, Jonathan J.; Kaye, Edward M.; Shanske, Sara; Sacconi, Sabrina; Tay, Stacey K.H.; DiMauro, Salvatore; Berry, Gerard T.

doi:10.1023/b:boli.0000045711.89888.5e

Cited by 20 publications

(13 citation statements)

References 19 publications

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“…41 Similarly, the predicted edge between DB04513 and RAF1 is substantiated by evidence that calmodulin 1, which is the target of experimental drug N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (DB04513), modulates signaling through the Ras/Raf/MEK/ERK signaling pathway. 42 Two additional edges between celiprolol and CYCS and between Reactome pathway 1454838 and transferrin were found to be biologically related through disease processes including hypertension, 43,44 and multiple myeloma. 45,46 The predicted edge between experimental drug 2-[formyl(hydroxy)amino]methyl-4-methylpentanoic acid (DB03683) and APAF1 was supported by their shared association with MMP9.…”

Section: Resultsmentioning

confidence: 99%

OWL-NETS: Transforming OWL Representations for Improved Network Inference

et al. 2017

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Our knowledge of the biological mechanisms underlying complex human disease is largely incomplete. While Semantic Web technologies, such as the Web Ontology Language (OWL), provide powerful techniques for representing existing knowledge, well-established OWL reasoners are unable to account for missing or uncertain knowledge. The application of inductive inference methods, like machine learning and network inference are vital for extending our current knowledge. Therefore, robust methods which facilitate inductive inference on rich OWL-encoded knowledge are needed. Here, we propose OWL-NETS (NEtwork Transformation for Statistical learning), a novel computational method that reversibly abstracts OWL-encoded biomedical knowledge into a network representation tailored for network inference. Using several examples built with the Open Biomedical Ontologies, we show that OWL-NETS can leverage existing ontology-based knowledge representations and network inference methods to generate novel, biologically-relevant hypotheses. Further, the lossless transformation of OWL-NETS allows for seamless integration of inferred edges back into the original knowledge base, extending its coverage and completeness.

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Section: Resultsmentioning

confidence: 99%

OWL-NETS: Transforming OWL Representations for Improved Network Inference

et al. 2017

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“…COX is a Cucontaining protein, and its activity changes in response to changes in Cu status. Under dietary Cu restriction condition, COX depression in the heart is one of the early biochemical alterations observed in rodents [26][27][28][29][30]. In pressure overload-induced cardiac hypertrophy, COX activities in the heart were also significantly depressed [1].…”

Section: Discussionmentioning

confidence: 99%

Cytochrome c Oxidase is Essential for Copper-Induced Regression of Cardiomyocyte Hypertrophy

et al. 2010

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Previous studies have shown that both copper (Cu) and vascular endothelial growth factor (VEGF) reduce the size of hypertrophic cardiomyocytes, but the Cu-induced regression is VEGF dependent. Studies in vivo have shown that hypertrophic cardiomyopathy is associated with a depression in cytochrome c oxidase (COX) activity, which could be involved in VEGF-mediated cellular function. The present study was undertaken to test the hypothesis that COX is a determinant factor in Cu-induced regression of cardiomyocyte hypertrophy. Primary cultures of neonatal rat cardiomyocytes were treated with phenylepherine (PE) at a final concentration of 100 microM in cultures for 48 h to induce cell hypertrophy. The hypertrophic cells were then treated with Cu sulfate at a final concentration of 5 microM in cultures for 24 h with a concomitant presence of PE to examine the effect of Cu on the regression of cardiomyocyte hypertrophy. Cell size changes were determined by flow cytometry, protein content, and molecular markers. Gene silencing was applied to study the effect of COX activity change on the regression of cardiomyocyte hypertrophy. PE treatment decreased COX activity in hypertrophic cardiomyocytes, and Cu addition restored the activity along with the regression of cell hypertrophy. Gene silencing using siRNA targeting COX-I significantly inhibited COX activity and blocked the Cu-induced regression of cell hypertrophy. VEGF alone also restored COX activity; but under the condition of COX inhibition by gene silencing, VEGF-induced regression of cell hypertrophy was suppressed. This study demonstrates that both Cu and VEGF can restore COX activity that is depressed in hypertrophic cardiomyocytes, and COX plays a determinant role in both Cu- and VEGF-induced regression of cardiomyocyte hypertrophy.

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“…Patients with mutations in complex-I have a 100-fold increased risk of severe demyelination secondary to multiple sclerosis (28). In lungs, pulmonary hypertension and right ventricular cardiomyopathy due to under-development of alveolar vasculature is one of the lethal presentations of congenital cytochrome C oxidase deficiency (29). Respiratory distress is a classical presentation of Stuve-Weidemann syndrome associated with partial deficiency of complex-I and complex-IV activities (30).…”

Section: Mitochondrial Dysfunction and Maturation Failure Of Lungs Anmentioning

confidence: 99%

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants

Ten

2016

Pediatr Res

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At birth, some organs in premature infants are not developed enough to meet challenges of the extra-uterine life. Although growth and maturation continues after premature birth, postnatal organ development may become sluggish or even arrested, leading to organ dysfunction. There is no clear mechanistic concept of this postnatal organ developmental failure in premature neonates. This review introduces a concept-forming hypothesis: Mitochondrial bioenergetic dysfunction is a fundamental mechanism of organs maturation failure in premature infants. Data collected in support of this hypothesis are relevant to two major diseases of prematurity: white matter injury and broncho-pulmonary dysplasia. In these diseases, totally different clinical manifestations are defined by the same biological process, developmental failure of the main functional units—alveoli in the lungs and axonal myelination in the brain. Although molecular pathways regulating alveolar and white matter maturation differ, proper bioenergetic support of growth and maturation remains critical biological requirement for any actively developing organ. Literature analysis suggests that successful postnatal pulmonary and white matter development highly depends on mitochondrial function which can be inhibited by sublethal postnatal stress. In premature infants, sublethal stress results mostly in organ maturation failure without excessive cellular demise.

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Congenital cardiomyopathy and pulmonary hypertension: Another fatal variant of cytochrome‐c oxidase deficiency

Cited by 20 publications

References 19 publications

OWL-NETS: Transforming OWL Representations for Improved Network Inference

OWL-NETS: Transforming OWL Representations for Improved Network Inference

Cytochrome c Oxidase is Essential for Copper-Induced Regression of Cardiomyocyte Hypertrophy

Mitochondrial dysfunction in alveolar and white matter developmental failure in premature infants

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