scholarly journals Accumulation of Carbonyl Proteins in the Brain of Mouse Model for Methylglyoxal Detoxification Deficits

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 574
Author(s):  
Shin Koike ◽  
Kazuya Toriumi ◽  
Sakura Kasahara ◽  
Yosuke Kibune ◽  
Yo-ichi Ishida ◽  
...  
Keyword(s):  
Creatine Kinase ◽  
Mass Spectrometry Analysis ◽  
Carbonyl Stress ◽  
Mitochondrial Creatine Kinase ◽  
Spectrometry Analysis ◽  
T Complex ◽  
Oxidative Damages ◽  
Carbonyl Protein ◽  
Arginine Residues ◽  
The Brain

Recent studies have shown that carbonyl stress is a causative factor of schizophrenia, categorized as carbonyl stress-related schizophrenia (CS-SCZ). However, the correlation between carbonyl stress and the pathogenesis of this disease is not well established. In this study, glyoxalase 1(Glo1)-knockout and vitamin B6-deficient mice (KO/VB6 (-) mice), which are susceptible to methylglyoxal (MGO)-induced oxidative damages, were used as a CS-SCZ model to analyze MGO-modified protein and the carbonyl stress status in the brain. A comparison between Wild/VB6(+) mice and KO/VB6(−) mice for accumulated carbonyl proteins levels, with several advanced glycation end products (AGEs) in the brain, revealed that carbonyl protein levels with the Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl) ornithine (MG-H1) moiety were significantly increased in the hippocampus, prefrontal cortex, striatum, cerebral cortex, and brainstem regions of the brain in KO/VB6(−) mice. Moreover, two-dimensional electrophoresis and Liquid chromatography-tandem mass spectrometry analysis showed MG-H1-modified arginine residues in mitochondrial creatine kinase, beta-adrenergic receptor kinase 1, and T-complex protein in the hippocampus region of KO/VB6(−) mice, but not in Wild/VB6(+) mice. In particular, MG-H1 modification of mitochondrial creatine kinase was quite notable. These results suggest that further studies focusing on MG-H1-modified and accumulated proteins in the hippocampus may reveal the onset mechanism of CS-SCZ induced by MGO-induced oxidative damages.

scholarly journals Large-scale identification of protein histidine methylation in human cells

2021 ◽  
Vol 3 (2) ◽  
Author(s):  
Sebastian Kapell ◽  
Magnus E Jakobsson
Keyword(s):  
Large Scale ◽  
Human Cells ◽  
System Level ◽  
Mass Spectrometry Analysis ◽  
Regulatory Function ◽  
Lysine Methylation ◽  
Spectrometry Analysis ◽  
Arginine Residues ◽  
Sequence Requirements ◽  
Level Analysis

Abstract Methylation can occur on histidine, lysine and arginine residues in proteins and often serves a regulatory function. Histidine methylation has recently attracted attention through the discovery of the human histidine methyltransferase enzymes SETD3 and METTL9. There are currently no methods to enrich histidine methylated peptides for mass spectrometry analysis and large-scale studies of the modification are hitherto absent. Here, we query ultra-comprehensive human proteome datasets to generate a resource of histidine methylation sites. In HeLa cells alone, we report 299 histidine methylation sites as well as 895 lysine methylation events. We use this resource to explore the frequency, localization, targeted domains, protein types and sequence requirements of histidine methylation and benchmark all analyses to methylation events on lysine and arginine. Our results demonstrate that histidine methylation is widespread in human cells and tissues and that the modification is over-represented in regions of mono-spaced histidine repeats. We also report colocalization of the modification with functionally important phosphorylation sites and disease associated mutations to identify regions of likely regulatory and functional importance. Taken together, we here report a system level analysis of human histidine methylation and our results represent a comprehensive resource enabling targeted studies of individual histidine methylation events.

scholarly journals Systemic inhibition of tissue-nonspecific alkaline phosphatase alters the brain-immune axis in experimental sepsis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Allison L. Brichacek ◽  
Stanley A. Benkovic ◽  
Sreeparna Chakraborty ◽  
Divine C. Nwafor ◽  
Wei Wang ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Endothelial Cells ◽  
Protective Role ◽  
Clinical Severity ◽  
Mass Spectrometry Analysis ◽  
Experimental Sepsis ◽  
Spectrometry Analysis ◽  
Severity Scores ◽  
Tissue Nonspecific Alkaline Phosphatase ◽  
The Brain

AbstractTissue-nonspecific alkaline phosphatase (TNAP) is a ubiquitous enzyme present in many cells and tissues, including the central nervous system. Yet its functions at the brain-immune axis remain unclear. The goal of this study was to use a novel small molecular inhibitor of TNAP, SBI-425, to interrogate the function of TNAP in neuroimmune disorders. Following intraperitoneal (IP) administration of SBI-425, mass spectrometry analysis revealed that the SBI-425 does not cross the blood-brain barrier (BBB) in healthy mice. To elucidate the role of TNAP at the brain-immune axis, mice were subjected to experimental sepsis and received either vehicle or SBI-425 (25 mg/kg, IP) daily for 7 days. While SBI-425 administration did not affect clinical severity outcomes, we found that SBI-425 administration suppressed CD4 + Foxp3+ CD25− and CD8 + Foxp3+ CD25− splenocyte T-cell populations compared to controls. Further evaluation of SBI-425’s effects in the brain revealed that TNAP activity was suppressed in the brain parenchyma of SBI-425-treated mice compared to controls. When primary brain endothelial cells were treated with a proinflammatory stimulus the addition of SBI-425 treatment potentiated the loss of barrier function in BBB endothelial cells. To further demonstrate a protective role for TNAP at endothelial barriers within this axis, transgenic mice with a conditional overexpression of TNAP were subjected to experimental sepsis and found to have increased survival and decreased clinical severity scores compared to controls. Taken together, these results demonstrate a novel role for TNAP activity in shaping the dynamic interactions within the brain-immune axis.

Arginine Methylation of Runx1 Regulates Its Biological and Transcriptional Activities.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2041-2041
Author(s):  
Xinyang Zhao ◽  
Animesh Parkanani ◽  
Jin Zhang ◽  
Richard Dunne ◽  
Andrew Xiao ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Arginine Methylation ◽  
Serine Phosphorylation ◽  
Context Dependency ◽  
Mass Spectrometry Analysis ◽  
Runt Domain ◽  
Spectrometry Analysis ◽  
Gene Reporter Assay ◽  
Arginine Residues

Abstract The AML1/Runx1 protein is required for definitive hematopoiesis and for the maturation of adult megakaryocytic cells. Alterations of the Runx1 gene by mutations, deletions and chromosome translocations are associated with several types of acute leukemia. Runx1 functions as both an activator and repressor of gene transcription with promoter and cell type context dependency. Likely, this relates to the ability of Runx1 to interact with a variety of transcription factors such as MEF, C/EBPa, Ets-1 and GATA-1 and also with repressor proteins such as Groucho, mSin3 and HDACs. Runx1 is post-translationally modified through acetylation and phosphorylation, and the acetylable and phosphorylable forms of Runx1 can activate transcription to higher level in Runx1 dependent reporter assays when HATs or Erk2 are coexpressed. Runx1 has also been shown to be methylated on lysine residues by SUV39H1 methyltransferase in fibroblasts. Based on the presence of a SGRGK motif in the runt domain of Runx1, we have been examining whether Runx1 is methylated on arginine residues by the protein arginine methyltransferases (PRMT). We have found that PRMT1 and PRMT5 are associated with Runx1 in AML cells by co-immunoprecipitation assays and using in vitro by GST-pulldown assays with in vitro translated PRMT(s) have shown that the interactions are direct. Using a luciferase gene reporter assay, we show that PRMT1 acts synergistically with p300 to activate Runx1 mediated transcription in response to cell proliferation signals. We have mapped the arginine methylation sites in Runx1 using GST-Runx1 fusion proteins, site-specific mutagenesis and mass spectrometry analysis. We have found three potential arginine methylation sites, one in the Runt domain, and two in the Runx1 carboxy-terminal region. Interestingly, one of these sites is in the region shown to interact with both the mSIN3A transcriptional repression complex and with p300. This suggests that arginine methylation of Runx1 may affects its transcriptional activating and repressing functions. Chromatin immunoprecipitation assays are underway to show how arginine methylation of Runx1 affects its activities in hematopoietic cells. Additional studies examining the effects of cross-talk between arginine methylation, lysine acetylation and serine phosphorylation has on Runx1 functions (biological and biochemical) will be presented.

scholarly journals Inhibitory Effects of Sodium Arsenite and Acacia Honey on Acetylcholinesterase in Rats

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Aliyu Muhammad ◽  
Oyeronke A. Odunola ◽  
Michael A. Gbadegesin ◽  
Abdullahi B. Sallau ◽  
Uche S. Ndidi ◽  
...  
Keyword(s):  
Ache Activity ◽  
Sodium Arsenite ◽  
Combined Treatment ◽  
Acetylcholinesterase Activity ◽  
Mass Spectrometry Analysis ◽  
Gas Chromatography Mass Spectrometry ◽  
Albino Rats ◽  
Spectrometry Analysis ◽  
Acacia Honey ◽  
The Brain

This study was conducted to investigate the effect of sodium arsenite and Acacia honey on acetylcholinesterase (AChE) activity and electrolytes in the brain and serum of Wistar rats. Male Wistar albino rats in four groups of five rats each were treated with distilled water, sodium arsenite (5 mg/kg body weight), Acacia honey (20% v/v), and sodium arsenite and Acacia honey, daily for one week. The sodium arsenite and Acacia honey significantlyP<0.05decreased AChE activity in the brain with the combined treatment being more potent. Furthermore, sodium arsenite and Acacia honey significantlyP<0.05decreased AChE activity in the serum. Strong correlation was observed between the sodium and calcium ion levels with acetylcholinesterase activity in the brain and serum. The gas chromatography mass spectrometry analysis of Acacia honey revealed the presence of a number of bioactive compounds such as phenolics, sugar derivatives, and fatty acids. These findings suggest that sodium arsenite and/or Acacia honey modulates acetylcholinesterase activities which may be explored in the management of Alzheimer’s diseases but this might be counteracted by the hepatotoxicity induced by arsenics.

scholarly journals Large-scale identification of protein histidine methylation in human cells

2021 ◽  
Author(s):  
Sebastian Kapell ◽  
Magnus E. Jakobsson
Keyword(s):  
Large Scale ◽  
Human Cells ◽  
System Level ◽  
Mass Spectrometry Analysis ◽  
Regulatory Function ◽  
Functional Importance ◽  
Spectrometry Analysis ◽  
Arginine Residues ◽  
Sequence Requirements ◽  
Level Analysis

ABSTRACTMethylation can occur on histidine, lysine and arginine residues in proteins and often serves a regulatory function. Histidine methylation has recently attracted notable attention through the discovery of the human histidine methyltransferase enzymes SETD3 and METTL9. There are currently no methods to enrich histidine methylated peptides for mass spectrometry analysis and large-scale analyses of the modification are hitherto absent. In the present study we query ultra-comprehensive proteomic datasets to generate a resource of histidine methylation sites in human cells. We use this resource to explore the frequency, localization, targeted domains, protein types and sequence requirements of histidine methylation and benchmark all analyses to methylation events on lysine and arginine. Our results demonstrate that histidine methylation is widespread in human cells and tissues and that the modification is over-represented in regions of mono-spaced histidine repeats. We also report colocalization of the modification with functionally important phosphorylation sites and disease associated mutations to identify regions of likely regulatory and functional importance. Taken together, we here report a system level analysis of human histidine methylation and our results represent a comprehensive resource enabling targeted studies of individual histidine methylation events.

Mitochondrial creatine kinase (EC 2.7.3.2) in the brain

1982 ◽  
Vol 119 (3) ◽  
pp. 209-223 ◽  
Author(s):  
R.A. Wevers ◽  
C.P.M. Reutelingsperger ◽  
B. Dam ◽  
J.B.J. Soons
Keyword(s):  
Creatine Kinase ◽  
Mitochondrial Creatine Kinase ◽  
The Brain

Application of Mass Spectrometry Methods to the Analysis of Lipid Composition of the Human Brain

2021 ◽  
Vol 37 (5) ◽  
pp. 80-87
Author(s):  
A.I. Tkachev ◽  
M.S. Osetrova ◽  
D.N. Smirnov ◽  
O.I. Efimova ◽  
E.E. Khrameev
Keyword(s):  
Mass Spectrometry ◽  
Human Brain ◽  
Lipid Composition ◽  
Large Scale ◽  
Lipid Extraction ◽  
Simultaneous Detection ◽  
Molecular Organization ◽  
Mass Spectrometry Analysis ◽  
Spectrometry Analysis ◽  
The Brain

Abstract-Lipids make up more than half of the dry matter of the human brain and play a key role in its functioning. However, the lipid composition of the brain anatomical structures remains poorly understood. The first such studies were carried out more than 50 years ago, but since then, a small number of works have been published describing the concentration of lipids in only a few areas of the human brain. A fundamentally new step towards understanding the molecular organization of the brain and identifying the molecular basis of human cognitive abilities should be a detailed large-scale study of the brain lipidome. However, there is no description in the literature of methods optimized for studying the lipid composition of the human brain. In this work, we develop and present methods for lipid extraction and mass spectrometry analysis, which ensure simultaneous detection of the maximum amount of different lipid classes and individual substances in the human brain, as well as the approaches to bioinformatics analysis of the obtained data. Their use makes it possible to create a comprehensive picture of the molecular organization of the human brain, which has no analogues in the world in terms of its completeness. Key words: lipidome, brain, mass spectrometry, high-performance liquid chromatography, bioinformatics The reported study was funded by the Russian Foundation for Basic Research, project no. 20-34-70077.

Sign in / Sign up

Export Citation Format

Share Document