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40
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Text
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URL Address
<a href="http://doi.org/10.1016/j.freeradbiomed.2017.04.022" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.freeradbiomed.2017.04.022</a>
Pages
595–609
Volume
108
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Differential protein acetylation assists import of excess SOD2 into mitochondria and mediates SOD2 aggregation associated with cardiac hypertrophy in the murine
Publisher
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Free radical biology & medicine
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-07
Subject
The topic of the resource
*Cardiac-specific transgenic mouse; *Mitochondria; *Mitochondrial translocation; *Protein acetylation; *Protein aggregation; *SOD2; Acetylation; Animals; Cardiomegaly/*metabolism; Cytosol/*metabolism; Heart/*physiology; Mice; Mitochondria/*metabolism; Pathological; Post-Translational; Protein Aggregation; Protein Folding; Protein Processing; Protein Transport; Reactive Oxygen Species/metabolism; Sirtuin 3/metabolism; Superoxide Dismutase/genetics/*metabolism; Transgenic
Creator
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Zhang Liwen; Chen Chwen-Lih; Kang Patrick T; Jin Zhicheng; Chen Yeong-Renn
Description
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SOD2 is the primary antioxidant enzyme neutralizing (*)O2(-) in mitochondria. Cardiac-specific SOD2 overexpression (SOD2-tg) induces supernormal function and cardiac hypertrophy in the mouse heart. However, the reductive stress imposed by SOD2 overexpression results in protein aggregation of SOD2 pentamers and differential hyperacetylation of SOD2 in the mitochondria and cytosol. Here, we studied SOD2 acetylation in SOD2-tg and wild-type mouse hearts. LC-MS/MS analysis indicated the presence of four acetylated lysines in matrix SOD2 and nine acetylated lysines in cytosolic SOD2 from the SOD2-tg heart. However, only one specific acetylated lysine residue was detected in the mitochondria of the wild-type heart, which was consistent with Sirt3 downregulation in the SOD2-tg heart. LC-MS/MS further detected hyperacetylated SOD2 with a signaling peptide in the mitochondrial inner membrane and matrix of the SOD2-tg heart, indicating partial arrest of the SOD2 precursor in the membrane during translocation into the mitochondria. Upregulation of HSP 70 and cytosolic HSP 60 enabled the translocation of excess SOD2 into mitochondria. In vitro acetylation of matrix SOD2 with Ac2O deaggregated pentameric SOD2, restored the profile of cytosolic SOD2 hyperacetylation, and decreased matrix SOD2 activity. As revealed by 3D structure, acetylation of K89, K134, and K154 of cytosolic SOD2 induces unfolding of the tertiary structure and breaking of the salt bridges that are important for the quaternary structure, suggesting that hyperacetylation and HSP 70 upregulation maintain the unfolded status of SOD2 in the cytosol and mediate the import of SOD2 across the membrane. Downregulation of Sirt3, HSP 60, and presequence protease in the mitochondria of the SOD2-tg heart promoted protein misfolding that led to pentameric aggregation.
Identifier
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<a href="http://doi.org/10.1016/j.freeradbiomed.2017.04.022" target="_blank" rel="noreferrer noopener">10.1016/j.freeradbiomed.2017.04.022</a>
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Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Cardiac-specific transgenic mouse
*Mitochondria
*Mitochondrial translocation
*Protein acetylation
*Protein aggregation
*SOD2
2017
Acetylation
Animals
Cardiomegaly/*metabolism
Chen Chwen-Lih
Chen Yeong-Renn
Cytosol/*metabolism
Department of Integrative Medical Sciences
Free radical biology & medicine
Heart/*physiology
Jin Zhicheng
Kang Patrick T
Mice
Mitochondria/*metabolism
NEOMED College of Medicine
Pathological
Post-Translational
Protein Aggregation
Protein Folding
Protein Processing
Protein Transport
Reactive Oxygen Species/metabolism
Sirtuin 3/metabolism
Superoxide Dismutase/genetics/*metabolism
Transgenic
Zhang Liwen
-
Text
A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text.
URL Address
<a href="http://doi.org/10.1007/s13361-017-1655-6" target="_blank" rel="noreferrer noopener">http://doi.org/10.1007/s13361-017-1655-6</a>
Pages
1392–1405
Issue
7
Volume
28
Dublin Core
The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/.
Title
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Gas-phase Reactivity of meta-Benzyne Analogs Toward Small Oligonucleotides of Differing Lengths.
Publisher
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Journal of the American Society for Mass Spectrometry
Date
A point or period of time associated with an event in the lifecycle of the resource
2017
2017-07
Subject
The topic of the resource
*Biradicals; *Ion-molecule reactions; *Mass spectrometry; *meta-Benzynes; *Oligonucleotides
Creator
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Widjaja Fanny; Max Joann P; Jin Zhicheng; Nash John J; Kenttamaa Hilkka I
Description
An account of the resource
The gas-phase reactivity of two aromatic carbon-centered sigma,sigma-biradicals (meta-benzyne analogs) and a related monoradical towards small oligonucleotides of differing lengths was investigated in a Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer coupled with laser-induced acoustic desorption (LIAD). The mono- and biradicals were positively charged to allow for manipulation in the mass spectrometer. The oligonucleotides were evaporated into the gas phase as intact neutral molecules by using LIAD. One of the biradicals was found to be unreactive. The reactive biradical reacts with dinucleoside phosphates and trinucleoside diphosphates mainly by addition to a nucleobase moiety followed by cleavage of the glycosidic bond, leading to a nucleobase radical (e.g., base-H) abstraction. In some instances, after the initial cleavage, the unquenched radical site of the biradical abstracts a hydrogen atom from the neutral fragment, which results in a net nucleobase abstraction. In sharp contrast, the related monoradical mainly undergoes facile hydrogen atom abstraction from the sugar moiety. As the size of the oligonucleotides increases, the rate of hydrogen atom abstraction from the sugar moiety by the monoradical was found to increase due to the presence of more hydrogen atom donor sites, and it is the only reaction observed for tetranucleoside triphosphates. Hence, the monoradical only attacks sugar moieties in these substrates. The biradical also shows significant attack at the sugar moiety for tetranucleoside triphosphates. This drastic change in reactivity indicates that the size of the oligonucleotides plays a key role in the outcome of these reactions. This finding is attributed to more compact conformations in the gas phase for the tetranucleoside triphosphates than for the smaller oligonucleotides, which result from stronger stabilizing interactions between the nucleobases. Graphical Abstract .
Identifier
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<a href="http://doi.org/10.1007/s13361-017-1655-6" target="_blank" rel="noreferrer noopener">10.1007/s13361-017-1655-6</a>
Rights
Information about rights held in and over the resource
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
*Biradicals
*Ion-molecule reactions
*Mass spectrometry
*meta-Benzynes
*Oligonucleotides
2017
Jin Zhicheng
Journal of the American Society for Mass Spectrometry
Kenttamaa Hilkka I
Max Joann P
Nash John J
Widjaja Fanny