scholarly journals Salicylaldehyde ester-mediated protein semi-synthesis enables studies on the tetra-acetylation of HMGB1

2021 ◽  
Author(s):  
Tongyao Wei ◽  
Jiamei Liu ◽  
Yi Tan ◽  
Ruohan Wei ◽  
Jinzheng Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
High Purity ◽  
Protein Function ◽  
Protein A ◽  
High Mobility ◽  
High Mobility Group ◽  
Biological Study ◽  
Post Translational Modifications ◽  
Site Specific ◽  
Synthesis Strategy

To answer how protein post-translational modifications (PTMs) affect protein function, conformation, sta-bility, localization and interaction with binders remains important in the biological study. However, the re-lated study has been dramatically hindered by the difficulty in obtaining homogenous proteins with site-specific PTMs of interest. Herein, we introduce a protein semi-synthesis strategy via salicylaldehyde ester-mediated chemical ligations (Ser/Thr ligation and Cys/Pen ligation). This methodology has enabled us to generate Lys (2/6/7/11) tetra-acetylated HMGB1 (high-mobility group box 1) protein, a 25 kDa proin-flammatory protein, in high purity. Further studies revealed that the tetra-acetylation may represent a regu-latory switch to control the HMGB1 signaling pathway by abolishing its interaction with lipopolysaccha-ride (LPS) and accelerating its degradation, consequently preventing cells from pyroptosis and lethality upon infectious injury.

The challenge of detecting modifications on proteins

2020 ◽  
Vol 64 (1) ◽  
pp. 135-153 ◽  
Author(s):  
Lauren Elizabeth Smith ◽  
Adelina Rogowska-Wrzesinska
Keyword(s):  
Mass Spectrometry ◽  
Protein Function ◽  
Chemical Properties ◽  
Lysine Acetylation ◽  
Mass Determination ◽  
Post Translational Modifications ◽  
Site Specific ◽  
The Common

Abstract Post-translational modifications (PTMs) are integral to the regulation of protein function, characterising their role in this process is vital to understanding how cells work in both healthy and diseased states. Mass spectrometry (MS) facilitates the mass determination and sequencing of peptides, and thereby also the detection of site-specific PTMs. However, numerous challenges in this field continue to persist. The diverse chemical properties, low abundance, labile nature and instability of many PTMs, in combination with the more practical issues of compatibility with MS and bioinformatics challenges, contribute to the arduous nature of their analysis. In this review, we present an overview of the established MS-based approaches for analysing PTMs and the common complications associated with their investigation, including examples of specific challenges focusing on phosphorylation, lysine acetylation and redox modifications.

scholarly journals Astragali Radix Contributes to the Inhibition of Liver Fibrosis via High-Mobility Group Box 1-Mediated Inflammatory Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jianxia Wen ◽  
Dan Wang ◽  
Jian Wang ◽  
Ruilin Wang ◽  
Shizhang Wei ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Signaling Pathway ◽  
Type I Collagen ◽  
Oral Treatment ◽  
High Mobility ◽  
High Mobility Group ◽  
Type I ◽  
Mrna Levels ◽  
Inflammatory Signaling ◽  
Astragali Radix

Astragali Radix (AR), the dried root of Astragali Radix membranaceus (Fisch.) Bge. or Astragali Radix membranaceus (Fisch.) Bge. var. mongholicus (Bge) Hsiao, is a commonly used traditional Chinese medicine for the treatment of liver diseases. This study aimed to comprehensively evaluate the pharmacological action and explore the potential mechanism of AR on liver fibrosis. Rats were administered with carbon tetrachloride for eight weeks, followed by oral treatment with AR for six weeks. The efficacy was confirmed by measuring liver function and liver fibrosis levels. The underlying mechanisms were explored by detecting the expression of related proteins. AR significantly decreased the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), collagen IV (COL-IV), hyaluronic acid (HA), laminin (LN), and precollagen type III (PCIII). In addition, AR inhibited the deposition of collagen and the activation of hepatic stellate cells. Those data strongly demonstrated that AR alleviated liver fibrosis by CCl4. In order to illustrate the potential inflammatory, the mRNA levels of IL-6, TNF-α, and IL-1β were detected. Subsequently, immunohistochemistry analysis was performed to further verify the expression of type I collagen. Finally, the expression of key proteins in the inflammatory signaling pathway was detected. AR significantly reduced the expression of high-mobility group box 1 (HMGB1), TLR4, Myd88, RAGE, and NF-κ B p65 genes and proteins. In addition, western blotting showed AR decreased the protein expression of RAGE, p-MEK1/2, p-ERK1/2, and p-c-Jun. Taken together, our data reveal that AR significantly inhibits liver fibrosis by intervening in the HMGB1-mediated inflammatory signaling pathway and secretion signaling pathway. This study will provide valuable references for the in-depth research and development of Astragali Radix against liver fibrosis.

Effect of SRY-Related High Mobility Group Box 9 on Extracellular Signal-Regulated Kinase/p38 Signaling Pathway in Glioma

2021 ◽  
Vol 11 (1) ◽  
pp. 171-175
Author(s):  
Tianlong Quan ◽  
Chunhua Zhang ◽  
Xin Song ◽  
Lu Wang
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Cell Invasion ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
High Mobility ◽  
Negative Control ◽  
Glioma Cell Line ◽  
High Mobility Group ◽  
Control Group

As a common malignant tumor in neurosurgery, glioma is characterized as high incidence rate, easy to invade, metastasize and recurrent. It is difficult to treat and has a poor prognosis. The gliomas pathogenesis is complex and has not been fully resolved. Therefore, finding effective molecular targets for glioma is beneficial to improve therapeutic effect. The SRY-related high mobility group box 9 (SOX9) gene involves in mammalian development and is significantly increased in glioma. However, SOX9’s role in gliomas is unclear. The glioma cell line U87 was assigned into control group, scramble group that was transfected with siRNA negative control, and SOX9 siRNA group that was transfected with SOX9 siRNA followed by analysis of SOX9 mRNA and protein level by qPCR and Western blot, cell proliferation by MTT assay, cell apoptosis by Caspase 3 activity assay, cell invasion by Transwell assay, and MMP-9 level by ELISA. SOX9 siRNA transfection significantly downregulated SOX9 mRNA and protein expressions, inhibited U87 cell proliferation, enhanced Caspase 3 activity, suppressed cell invasion of U87, decreased the secretion of MMP-9 in the supernatant, and reduced ERK1/2 and P38 phosphorylation levels (P < 0.05). SOX9 can regulate the progression of glioma by regulating ERK/P38 signaling pathway, promoting cell apoptosis, inhibiting cell proliferation, and restraining cell invasion.

Does high mobility group 1 protein function as a late mediator for LPS- or TNF-induced shock in galactosamine-sensitized mice?

2002 ◽  
Vol 8 (5) ◽  
pp. 391-398 ◽  
Author(s):  
Ryoichi Hasunuma ◽  
Hiroko Maruyama ◽  
Hiroaki Takimoto ◽  
Roland Ryll ◽  
Shigenori Tanaka ◽  
...  
Keyword(s):  
Protein Function ◽  
High Mobility ◽  
High Mobility Group ◽  
Group 1

The interaction between ORC and the high mobility group protein HMGA1a creates site-specific replication origins

2008 ◽  
Vol 2008 (Spring) ◽  
Author(s):  
Aloys Schepers ◽  
Andreas Thomae ◽  
Dagmar Pich ◽  
Jan Brocher ◽  
Christian Berens ◽  
...  
Keyword(s):  
High Mobility ◽  
High Mobility Group ◽  
Replication Origins ◽  
High Mobility Group Protein ◽  
Site Specific ◽  
Group Protein

High-mobility group box-1 protein activates inflammatory signaling pathway components and disrupts retinal vascular-barrier in the diabetic retina

2013 ◽  
Vol 107 ◽  
pp. 101-109 ◽  
Author(s):  
Ghulam Mohammad ◽  
Mohammad Mairaj Siddiquei ◽  
Amira Othman ◽  
Mohamed Al-Shabrawey ◽  
Ahmed M. Abu El-Asrar
Keyword(s):  
Signaling Pathway ◽  
High Mobility ◽  
High Mobility Group ◽  
Inflammatory Signaling ◽  
Diabetic Retina
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