Difference between revisions of "Albertini 2012 Abstract Bioblast"
| Line 7: | Line 7: | ||
|abstract=[[File:Eva albertini.jpg|right|150px|Eva Albertini]] | |abstract=[[File:Eva albertini.jpg|right|150px|Eva Albertini]] | ||
Availability of methionine is known to modulate the rate of aging in model organisms, best illustrated by the observation that dietary methionine restriction extends the lifespan of rodents. However, the underlying mechanisms are incompletely understood. In eukaryotic cells, methionine can be converted to cysteine through the reverse transsulfuration pathway thereby modulating intracellular methionine availability. Whereas previous results obtained in yeast and fruit flies suggest that alterations in the reverse transsulfuration pathway modulate the rate of aging, it is not known whether this function is conserved in evolution. Here we show that depletion of cystathionine beta synthase (CBS), a rate limiting enzyme in the reverse transsulfuration pathway, induces premature senescence in human endothelial cells. We found that CBS depletion induces mild mitochondrial dysfunction and increases the sensitivity of endothelial cells to homocysteine, a known inducer of endothelial cell senescence and an established risk factor for vascular disease. Our finding that CBS deficiency induces endothelial cell senescence in vitro, involving both mitochondrial dysfunction and increased susceptibility of the cells to homocysteine, suggests a new mechanism linking CBS deficiency to vascular aging and disease. | Availability of methionine is known to modulate the rate of aging in model organisms, best illustrated by the observation that dietary methionine restriction extends the lifespan of rodents. However, the underlying mechanisms are incompletely understood. In eukaryotic cells, methionine can be converted to cysteine through the reverse transsulfuration pathway thereby modulating intracellular methionine availability. Whereas previous results obtained in yeast and fruit flies suggest that alterations in the reverse transsulfuration pathway modulate the rate of aging, it is not known whether this function is conserved in evolution. Here we show that depletion of cystathionine beta synthase (CBS), a rate limiting enzyme in the reverse transsulfuration pathway, induces premature senescence in human endothelial cells. We found that CBS depletion induces mild mitochondrial dysfunction and increases the sensitivity of endothelial cells to homocysteine, a known inducer of endothelial cell senescence and an established risk factor for vascular disease. Our finding that CBS deficiency induces endothelial cell senescence in vitro, involving both mitochondrial dysfunction and increased susceptibility of the cells to homocysteine, suggests a new mechanism linking CBS deficiency to vascular aging and disease. | ||
* [[Albertini 2012 Aging (Albany NY)]] | * [[Albertini 2012 Aging (Albany NY)|Albertini E, Kozieล R, Duerr A, Neuhaus M, Jansen-Duerr P (2012) Cystathionine beta synthase modulates senescence of human endothelial cells. Aging (Albany NY) (Epub ahead of print)]] | ||
|keywords=Methionine, Cysteine, Aging, HUVEC, Cystathionine beta synthase | |keywords=Methionine, Cysteine, Aging, HUVEC, Cystathionine beta synthase | ||
|mipnetlab=AT Innsbruck Jansen-Duerr P, | |mipnetlab=AT Innsbruck Jansen-Duerr P, | ||
| Line 30: | Line 30: | ||
Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10,ย 6020 Innsbruck, Austria - e-mail: [email protected] | Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10,ย 6020 Innsbruck, Austria - e-mail: [email protected] | ||
== Help == | == Help == | ||
* [[Abstracts help]] | * [[Abstracts help]] | ||
* [[MitoPedia Glossary: Terms and abbreviations]] | * [[MitoPedia Glossary: Terms and abbreviations]] | ||
Revision as of 11:16, 22 November 2012
| Albertini E, Koziel R, Duerr A, Neuhaus M, Jansen-Duerr P (2012) Cystathionine beta synthase modulates senescence of human endothelial cells. Mitochondr Physiol Network 17.12. |
Link: MiPNet17.12 Bioblast 2012 - Open Access
Albertini E, Koziel R, Duerr A, Neuhaus M, Jansen-Duerr P (2012)
Event: Bioblast 2012
Availability of methionine is known to modulate the rate of aging in model organisms, best illustrated by the observation that dietary methionine restriction extends the lifespan of rodents. However, the underlying mechanisms are incompletely understood. In eukaryotic cells, methionine can be converted to cysteine through the reverse transsulfuration pathway thereby modulating intracellular methionine availability. Whereas previous results obtained in yeast and fruit flies suggest that alterations in the reverse transsulfuration pathway modulate the rate of aging, it is not known whether this function is conserved in evolution. Here we show that depletion of cystathionine beta synthase (CBS), a rate limiting enzyme in the reverse transsulfuration pathway, induces premature senescence in human endothelial cells. We found that CBS depletion induces mild mitochondrial dysfunction and increases the sensitivity of endothelial cells to homocysteine, a known inducer of endothelial cell senescence and an established risk factor for vascular disease. Our finding that CBS deficiency induces endothelial cell senescence in vitro, involving both mitochondrial dysfunction and increased susceptibility of the cells to homocysteine, suggests a new mechanism linking CBS deficiency to vascular aging and disease.
โข Keywords: Methionine, Cysteine, Aging, HUVEC, Cystathionine beta synthase
โข O2k-Network Lab: AT Innsbruck Jansen-Duerr P
Labels:
Stress:Mitochondrial Disease; Degenerative Disease and Defect"Mitochondrial Disease; Degenerative Disease and Defect" 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., Aging; Senescence"Aging; Senescence" 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: Human Tissue;cell: Endothelial; Epithelial; Mesothelial Cell"Endothelial; Epithelial; Mesothelial Cell" 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.
Regulation: Membrane Potential"Membrane Potential" 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.
Coupling state: LEAK, ROUTINE, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property.
HRR: Oxygraph-2k
Affiliations and author contributions
Institute for Biomedical Aging Research, University of Innsbruck, Rennweg 10, 6020 Innsbruck, Austria - e-mail: [email protected]
