Difference between revisions of "Kim MiP2010"
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|authors=Kim HK, Park WS, Choi SW, Ha SH, Kim N, Han J | |authors=Kim HK, Park WS, Choi SW, Ha SH, Kim N, Han J | ||
|year=2010 | |year=2010 | ||
|abstract=Tetrahydrobiopterin (BH4) is an endogenous essential cofactor for NO synthesis and metabolisms of phenylalanine, tyrosine and tryptophan. To gain a better understanding of how BH4 orchestrate the biological processes in mitochondria and control phenotypic characteristics of an organism, we investigated the BH4 deficiency effect on cardiac mitochondria function and proteomic alteration in sepiapterin reductase gene knock out mouse (Spr-/-) which has severe BH4 deficiency. Spr-/- mouse was shown typical growth retardation induced by BH4 deficiency compared to wild type control mouse. The cardiac mitochondrial morphology alterations in both size and number were observed under electron microscopy. As a systemic approach to evaluate global proteomic modifications in cardiac mitochondria from BH4 deficiency model, we performed 2DE and LC-MS/MS proteomic analysis. We then performed data integrative analysis to systematically validate and organize them into significantly altered biological pathways. Our results suggested that altered proteins in BH4 deficiency induced mitochondrial dysfunction by affecting two major key factors in mitochondria metabolism, the TCA cycle and electron transport system. The systemic prediction was evaluated with various functional validations. The decrease of mitochondrial nitric oxide (mtNO) and increase of ROS production in Spr-/- mouse which induced oxidative damage on mitochondrial function accompanied with mitochondrial membrane potential (ฮฮจmt) depolarization, mitochondria respiration rate inhibition and mitochondrial DNA fragmentation. These findings suggest new insights into BH4 as a novel regulator of mitochondrial function. | |abstract=Tetrahydrobiopterin (BH4) is an endogenous essential cofactor for NO synthesis and metabolisms of phenylalanine, tyrosine and tryptophan. To gain a better understanding of how BH4 orchestrate the biological processes in mitochondria and control phenotypic characteristics of an organism, we investigated the BH4 deficiency effect on cardiac mitochondria function and proteomic alteration in sepiapterin reductase gene knock out mouse (Spr-/-) which has severe BH4 deficiency. Spr-/- mouse was shown typical growth retardation induced by BH4 deficiency compared to wild type control mouse. The cardiac mitochondrial morphology alterations in both size and number were observed under electron microscopy. As a systemic approach to evaluate global proteomic modifications in cardiac mitochondria from BH4 deficiency model, we performed 2DE and LC-MS/MS proteomic analysis. We then performed data integrative analysis to systematically validate and organize them into significantly altered biological pathways. Our results suggested that altered proteins in BH4 deficiency induced mitochondrial dysfunction by affecting two major key factors in mitochondria metabolism, the TCA cycle and electron transport system. The systemic prediction was evaluated with various functional validations. The decrease of mitochondrial nitric oxide (mtNO) and increase of ROS production in Spr-/- mouse which induced oxidative damage on mitochondrial function accompanied with mitochondrial membrane potential (ฮฮจmt) depolarization, mitochondria respiration rate inhibition and mitochondrial DNA fragmentation. These findings suggest new insights into BH4 as a novel regulator of mitochondrial function. | ||
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Revision as of 18:40, 9 March 2011
| Kim HK, Park WS, Choi SW, Ha SH, Kim N, Han J (2010) BH4 deficiency involved in cardiac mitochondria metabolic pathway remodelling. Mitochondr. Physiol. Network 15.6: 58. |
Kim HK, Park WS, Choi SW, Ha SH, Kim N, Han J (2010)
Abstract: Tetrahydrobiopterin (BH4) is an endogenous essential cofactor for NO synthesis and metabolisms of phenylalanine, tyrosine and tryptophan. To gain a better understanding of how BH4 orchestrate the biological processes in mitochondria and control phenotypic characteristics of an organism, we investigated the BH4 deficiency effect on cardiac mitochondria function and proteomic alteration in sepiapterin reductase gene knock out mouse (Spr-/-) which has severe BH4 deficiency. Spr-/- mouse was shown typical growth retardation induced by BH4 deficiency compared to wild type control mouse. The cardiac mitochondrial morphology alterations in both size and number were observed under electron microscopy. As a systemic approach to evaluate global proteomic modifications in cardiac mitochondria from BH4 deficiency model, we performed 2DE and LC-MS/MS proteomic analysis. We then performed data integrative analysis to systematically validate and organize them into significantly altered biological pathways. Our results suggested that altered proteins in BH4 deficiency induced mitochondrial dysfunction by affecting two major key factors in mitochondria metabolism, the TCA cycle and electron transport system. The systemic prediction was evaluated with various functional validations. The decrease of mitochondrial nitric oxide (mtNO) and increase of ROS production in Spr-/- mouse which induced oxidative damage on mitochondrial function accompanied with mitochondrial membrane potential (ฮฮจmt) depolarization, mitochondria respiration rate inhibition and mitochondrial DNA fragmentation. These findings suggest new insights into BH4 as a novel regulator of mitochondrial function.
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Stress:RONS; Oxidative Stress"RONS; Oxidative Stress" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property., Genetic Defect; Knockdown; Overexpression"Genetic Defect; Knockdown; Overexpression" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. Organism: Mouse Tissue;cell: Cardiac Muscle"Cardiac Muscle" is not in the list (Heart, Skeletal muscle, Nervous system, Liver, Kidney, Lung;gill, Islet cell;pancreas;thymus, Endothelial;epithelial;mesothelial cell, Blood cells, Fat, ...) of allowed values for the "Tissue and cell" property.
Enzyme: TCA Cycle and Matrix Dehydrogenases"TCA Cycle and Matrix Dehydrogenases" is not in the list (Adenine nucleotide translocase, Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase, Inner mt-membrane transporter, Marker enzyme, Supercomplex, TCA cycle and matrix dehydrogenases, ...) of allowed values for the "Enzyme" property. Regulation: Respiration; OXPHOS; ETS Capacity"Respiration; OXPHOS; ETS Capacity" is not in the list (Aerobic glycolysis, ADP, ATP, ATP production, AMP, Calcium, Coupling efficiency;uncoupling, Cyt c, Flux control, Inhibitor, ...) of allowed values for the "Respiration and regulation" property.
