In Vivo Formation and in Vitro Replication of a Guanine−Thymine Intrastrand Cross-Link Lesion†

Biochemistry ◽  
2007 ◽  
Vol 46 (44) ◽  
pp. 12757-12763 ◽  
Author(s):  
Yong Jiang ◽  
Haizheng Hong ◽  
Huachuan Cao ◽  
Yinsheng Wang
Keyword(s):  
Cross Link ◽  
In Vitro Replication

scholarly journals Cross-linking modifications of HDL apoproteins by oxidized phospholipids: structural characterization, in vivo detection, and functional implications

2020 ◽  
Vol 295 (7) ◽  
pp. 1973-1984
Author(s):  
Detao Gao ◽  
Mohammad Z. Ashraf ◽  
Lifang Zhang ◽  
Niladri Kar ◽  
Tatiana V. Byzova ◽  
...  
Keyword(s):  
Density Lipoprotein ◽  
Cross Linking ◽  
Oxidized Phospholipids ◽  
Cross Link ◽  
In Vivo Detection ◽  
Lysine Residues ◽  
Cross Links ◽  
Human Atheroma

Apolipoprotein A-I (apoA-I) is cross-linked and dysfunctional in human atheroma. Although multiple mechanisms of apoA-I cross-linking have been demonstrated in vitro, the in vivo mechanisms of cross-linking are not well-established. We have recently demonstrated the highly selective and efficient modification of high-density lipoprotein (HDL) apoproteins by endogenous oxidized phospholipids (oxPLs), including γ-ketoalkenal phospholipids. In the current study, we report that γ-ketoalkenal phospholipids effectively cross-link apoproteins in HDL. We further demonstrate that cross-linking impairs the cholesterol efflux mediated by apoA-I or HDL3 in vitro and in vivo. Using LC-MS/MS analysis, we analyzed the pattern of apoprotein cross-linking in isolated human HDL either by synthetic γ-ketoalkenal phospholipids or by oxPLs generated during HDL oxidation in plasma by the physiologically relevant MPO-H2O2-NO2− system. We found that five histidine residues in helices 5–8 of apoA-I are preferably cross-linked by oxPLs, forming stable pyrrole adducts with lysine residues in the helices 3–4 of another apoA-I or in the central domain of apoA-II. We also identified cross-links of apoA-I and apoA-II with two minor HDL apoproteins, apoA-IV and apoE. We detected a similar pattern of apoprotein cross-linking in oxidized murine HDL. We further detected oxPL cross-link adducts of HDL apoproteins in plasma and aorta of hyperlipidemic LDLR−/− mice, including cross-link adducts of apoA-I His-165–apoA-I Lys-93, apoA-I His-154–apoA-I Lys-105, apoA-I His-154–apoA-IV Lys-149, and apoA-II Lys-30–apoE His-227. These findings suggest an important mechanism that contributes to the loss of HDL's atheroprotective function in vivo.

scholarly journals 1182 PROTEASE ANATAGONISTS INHIBIT THE IN VIVO AND IN VITRO REPLICATION OF ROTAVIRUS

1985 ◽  
Vol 19 (4) ◽  
pp. 307A-307A ◽  
Author(s):  
Robert H Yolken ◽  
Joseph E Eiden ◽  
Steven Vonderfecht ◽  
Richard Tidwell ◽  
Dieter Geratz
Keyword(s):  
In Vitro Replication

scholarly journals Inhibition of ATR-Dependent Signaling by Protoapigenone and Its Derivative Sensitizes Cancer Cells to Interstrand Cross-link–Generating Agents In Vitro and In Vivo

2012 ◽  
Vol 11 (7) ◽  
pp. 1443-1453 ◽  
Author(s):  
Hui-Chun Wang ◽  
Alan Yueh-Luen Lee ◽  
Wen-Cheng Chou ◽  
Chin-Chung Wu ◽  
Chao-Neng Tseng ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cross Link

scholarly journals Sam68 binds Alu-rich introns in SMN and promotes pre-mRNA circularization

2019 ◽  
Vol 48 (2) ◽  
pp. 633-645 ◽  
Author(s):  
Vittoria Pagliarini ◽  
Ariane Jolly ◽  
Pamela Bielli ◽  
Valentina Di Rosa ◽  
Pierre De la Grange ◽  
...  
Keyword(s):  
Binding Sites ◽  
Muscular Atrophy ◽  
Circular Rna ◽  
Cross Link ◽  
Bioinformatics Analyses ◽  
Protein Coding ◽  
Inverted Orientation ◽  
Human Genes

Abstract The Spinal Muscular Atrophy (SMA) gene SMN was recently duplicated (SMN1 and SMN2) in higher primates. Furthermore, invasion of the locus by repetitive elements almost doubled its size with respect to mouse Smn, in spite of an almost identical protein-coding sequence. Herein, we found that SMN ranks among the human genes with highest density of Alus, which are evolutionary conserved in primates and often occur in inverted orientation. Inverted repeat Alus (IRAlus) negatively regulate splicing of long introns within SMN, while promoting widespread alternative circular RNA (circRNA) biogenesis. Bioinformatics analyses revealed the presence of ultra-conserved Sam68 binding sites in SMN IRAlus. Cross-link-immunoprecipitation (CLIP), mutagenesis and silencing experiments showed that Sam68 binds in proximity of intronic Alus in the SMN pre-mRNA, thus favouring circRNA biogenesis in vitro and in vivo. These findings highlight a novel layer of regulation in SMN expression, uncover the crucial impact exerted by IRAlus and reveal a role for Sam68 in SMN circRNA biogenesis.

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