Research progress on mechanism and protein modification of Beclin1 in autophagy / 中国生物制品学杂志

@#Autophagy is a process of self-phagocytosis of lysosomal degrading substances in cells. Under normal conditions,cells can use autophagy to remove their own garbage to provide energy,while in a state of stress,autophagy can also be activated,resulting in cell damage and death,which can seriously lead to cancer. B-cell lymphoma-2-interacting myosin-like coiled-coil protein(Beclin1) is a central node in the autophagy pathway and interacts with a variety of proteins to regulate the formation and maturation of autophagosomes. Kinase mediates the protein modification of Beclin1 during autophagy,which will affect its activity and interaction with other autophagy-related proteins. Beclin1 is closely related to the occurrence and development of tumors. Therefore,this paper focused on the research progress on the mechanism and protein modification of Beclin1 in autophagy,in view to providing a reference for the research of targeted drugs of tumor autophagy.

Research progress in mechanism of high mobility group box 1 regulating inflammatory response / 中华创伤杂志

Inflammatory reaction dominated by defense response will arise against infection and trauma. As an important proinflammatory cytokine, high mobility group box 1 (HMGB1) is widely expressed in all nuclear cells to mediate the inflammatory response. However, the biological functions of HMGB1 in inflammation vary depending on the type of HMGB1 protein modification and the localization in the cell. HMGB1 protein will be modified as acetylation of lysine residues, methylation of lysine residues, oxidation of cysteine residues, phosphorylation of serine residues, glycosylation of asparagine residues, adenosine diphosphate-ribosylation and lactylation of the protein in the nucleus, migrate from the nucleus to the cytoplasm, and release into the extracellular compartment. Extracellular HMGB1 can bind to receptors for advanced glycation end products (RAGE) and Toll-like receptors, activate cells and regulate inflammatory responses. The authors review the research progress in regulatory mechanism of HMGB1 in inflammation response from aspects of its post-translational modifications, releases, biological roles and binding receptors, hoping to provide theoretical basis for finding the targets of inflammation intervention.

Emerging role of protein modification in inflammatory bowel disease / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The onset of inflammatory bowel disease (IBD) involves many factors, including environmental parameters, microorganisms, and the immune system. Although research on IBD continues to expand, the specific pathogenesis mechanism is still unclear. Protein modification refers to chemical modification after protein biosynthesis, also known as post-translational modification (PTM), which causes changes in the properties and functions of proteins. Since proteins can be modified in different ways, such as acetylation, methylation, and phosphorylation, the functions of proteins in different modified states will also be different. Transitions between different states of protein or changes in modification sites can regulate protein properties and functions. Such modifications like neddylation, sumoylation, glycosylation, and acetylation can activate or inhibit various signaling pathways (e.g., nuclear factor-‍κB (NF-‍κB), extracellular signal-regulated kinase (ERK), and protein kinase B (AKT)) by changing the intestinal flora, regulating immune cells, modulating the release of cytokines such as interleukin-1β (IL-‍‍1β), tumor necrosis factor-α (TNF‍-‍α), and interferon-‍γ (IFN-‍γ), and ultimately leading to the maintenance of the stability of the intestinal epithelial barrier. In this review, we focus on the current understanding of PTM and describe its regulatory role in the pathogenesis of IBD.

Function of TRPM8 Ion Channel and Regulation Mechanism of Its Post-translational Modification / 中国生物化学与分子生物学报

TRPM8 (transient receptor potential melastatin 8), also known as a cold and menthol receptor and a member of the TRP (transient receptor potential) channel superfamily, locates on the cell membrane or organelle membrane.. TRPM8 is a non-selective cation channel, which can be used as either a cold and heat sensor or cold and pain sensor to conduct signal transduction. It plays an important role in maintaining intracellular homeostasis and controlling ion in cells. It has been found that PTM (post-translational modification) of TRPM8 affects the occurrence and development of many diseases by regulating the function of TRPM8 channel. Therefore, it is necessary to explore the PTM process of TRPM8 to gain a deeper understanding for the function and regulatory mechanism of TRPM8. At present, several types of post-translational modifications of TRPM8 have been reported, including phosphorylation, ubiquitination and glycosylation, which can regulate protein interactions and change the activity of TRPM8 ion channels, leading to modulation of cell proliferation, migration and apoptosis. It is noteworthy that the expression of TRPM8 level is closely related to many kinds of cancers, such as prostate cancer, bladder cancer and breast cancer. This review focus on the structure of TRPM8 ion channels, systematically elaborate the translational modifications, activator and antagonist of TRPM8 protein, and the regulation of some proteins on TRPM8 channel activity. At the same time, we summarize the recent progress of TRPM8 in prostate cancer, bladder cancer and breast cancer, which would provide new directions and new ideas for the treatment of cancer.

Research progress of reactive nitrogen species on cell protection and injury / 药学学报

Reactive nitrogen species (RNS) affects intracellular redox balance and induces post-translational modification of proteins. Moreover, RNS, as the signal molecule, participates in the transduction of cellular signals under physiological conditions. However, excessive RNS can induce nitrosative stress and then damage cells, and thereby may play a role in the tumor initiation and progression. Thus, we discussed the role of RNS under physiological conditions and the tumor microenvironment, which may provide some novel ideas for the development of new drugs and the treatment of diseases.

Advances and applications of lysine acetylation / 药学学报

Protein acetylation is a process of adding an acetyl group to a protein lysine residue with the help of acetyltransferase, which is a pivotal protein post-translational modification linking acetyl-CoA metabolism and cell signal transduction. Recently, the development of mass spectrometry has deepened our understanding of lysine acetylation. Lysine acetylation is involved in many processes such as gene transcription, protein degradation, cellular metabolism, and stress response, which affects biological processes by regulating protein interactions, activity, stability and localization. Protein acetylation is widely happened and plays important regulatory roles in a diversity of human diseases such as metabolic diseases, tumors and cardiovascular diseases. Besides, deacetylase inhibitors have displayed a great potential in the treatment of various diseases especially tumors and metabolic associated diseases. In this review, we summarized the advances and application of acetylation, and discussed the remaining problems in this area.

Effect of β-asarone on differential protein expression in brain tissue of APPswe/PSldE9 double transgenic mice / 第二军医大学学报

Objective To investigate the effect of β-asarone on differential protein expression in brain tissue of APPswe/PS1dE9 double transgenic mice, and to explore its mechanism in treatment of Alzheimer disease (AD). Methods The animals were divided into normal control group (C57BL/6J mice), model group (APPswe/PS1dE9 mice) and β-asarone treatment group (APPswe/PS1dE9 mice), with ten mice in each group. In a period of 90 days, the mice in β-asarone treatment group were administered with β-asarone by intragastric gavage (15 mg/[kg·d]), and the mice in normal control and model groups were administered with equal doses of normal saline. The learning and memory abilities of mice were detected by Morris water maze test. The expression of β-amyloid precursor protein (APP) in brain tissues was detected by immunohistochemistry. Proteomics analysis of brain tissues was performed by isobaric tags for relative and absolute quantification (iTRAQ). The expression of differential protein H2A and H2B was identified by Western blotting. Results Compared with the model group, the escape latency and the first latency time required to find the escaped platform of mice in the β-asarone treatment group were significantly shortened (P<0.05), the across-platform times were significantly increased (P<0.05), the expression of APP was significantly decreased (P<0.05), and the expressions of H2A 1-H, H2B 2-E and H2B 1-F/J/L were significantly decreased (P<0.05). Conclusion β-Asarone plays a therapeutic role by intervening the modification of histone, which might be one of the mechanisms to improve learning and memory abilities injured by the toxicity of β-amyloid peptide.

Research strategy of traditional Chinese medicine proteomics / 中国中药杂志

The application of proteomics in the research of traditional Chinese medicine (TCM) is very extensive, and there have been many successful cases. In this paper, the previous studies on the complex system of TCM by using proteomics technology were reviewed, and the authors proposed to set up a special subject on proteomics in TCM, which is called TCM proteomics. In this paper, the research strategies and the future research directions of TCM proteomics were reviewed and discussed, which may provide some ideas for the researchers of TCM proteomics.

Role of O-GlcNAc protein modification in attenuation of brain damage by glutamine in septic rats / 中华麻醉学杂志

Objective To evaluate the role of O-GlcNAc protein modification in attenuation of brain damage by glutamine in septic rats.Methods Sixty male SD rata weighing 180-240 g were randomly divided into 4 groups:sham operation group(group S,n =12),sepsis group(group CLP,n =16),glutamine group(group G,n =16),an inhibitor of O-linked-N-acetyl glucosamine transferase Alloxan + glutamine group(group G + A,n =16).Rats were submitted to sepsis by cecal ligation and perforation(CLP).Glutamine(Gln)0.75 g/kg was injected iv after CLP in group G.Gln 0.75 g/kg was injected iv and Alloxan 90 mg/kg was injected ip after CLP in group G + A.Equal volume of normal saline was given in group S and group CLP.A1 24 h afler CLP,the neural reflex score was evaluated,then rat was sacrificed.The brain was removed for measurement of brain water content,observation of histopathology and determination of O-GlcNAc-modified protein expression.Results Compared with group S,neural reflex score and brain water content were significantly increased in groups CLP,G and G + A(P ＜ 0.05).Compared with group CLP,neural reflex score and brain water content were significantly decreased in groups G and G + A(P ＜ 0.05),and the expression of O-GlcNAc-modified protein was upregulated in group G(P ＜ 0.05),Compared with groups G,neural reflex score and brain water content were significantly increased,and the expression of O-GlcNAc-modified protein downregulated in group G + A(P ＜ 0.05).There was no significant difference in O-GlcNAc-modified protein expression among groups S,CLP and G + A.Conclusion Glutamine attenuates brain damage through O-GlcNAc protein modification in septic rats.

Role of protein O-linked N-acetyl-glucosamine modification in glutamine-induced improvement in vascular hyporeactivity in rats with septic shock / 中华麻醉学杂志

Objective To investigate the role of protein O-linked N-acetyl-glucosamine (O-GlcNAc) modification in glutamine-induced improvement in the vascular hyporeactivity in rats with septic shock.Methods Thirty-two adult male Sprague-Dawley rats,aged 2-3 months,weighing 250-300 g,were randomly divided into 4 groups (n =8 each):sham operation group (S group); septic shock group (C group); glutamine group (G group) ; alloxan group (A group).Septic shock was induced by cecal ligation and puncture (CLP).In G and A groups,glutamine 0.75 g/kg was infused intravenously over 30 min at 1 h before CLP,and in addition alloxan 90 mg/kg was infused intraperitoneally in A group.Phenylephrine (PE) 0.5,1.0,2.0,and 2.5 μg/kg was injected intravenously at 20 min intervals at 6 h after CLP and the percentage increase in mean arterial pressure (MAP) was calculated.The thoracic aorta rings were isolated to perform the isolated vascular tension experiment.The concentration-response curve of PE was obtained in tension experiments,and the PE maximum efficacy (Emas) and median effective dose ( EC50 ) were calculated.The expression of O-GlcNAc modification and iNOS content in the thoracic aorta were detected in all groups.Blood samples were taken to determine the serum concentration of NO.Results Compared with S group,the percentage increase in MAP and Emax were significantly decreased,while the EC50,serum concentration of NO,and expression of O-GlcNAc modification and iNOS content in thoracic aorta were significantly increased in C,G and A groups ( P ＜ 0.05).Compared with C group,the expression of O-GlcNAc modification in the thoracic aorta was significantly increased,and EC50 was significantly decreased in G group,and the percentage increase in MAP and Emax were significantly increased,while the serum concentration of NO,and content of iNOS in the thoracic aorta were significantly decreased in G and A groups ( P ＜ 0.05).Compared with G group,the EC50,serum concentration of NO,and content of iNOS in the thoracic aorta were significantly increased,while the percentage increase in MAP,Emax and expression of O-GlcNAc modification in the thoracic aorta were significantly decreased ( P ＜ 0.05 ).Conclusion Glutamine improves the vascular hyporeactivity through increasing the level of protein O-GlcNAc modification in rats with septic shock.

Paracoccidioides brasiliensis translation and protein fate machineries revealed by functional genome analysis

The translational and post-translational modification machineries of Paracoccidioides brasiliensis were assessed by means of comparative analyses of PbAESTs (P. brasiliensis assembled expressed sequence tags) with sequences deposited on different databases. Of the 79 sequences corresponding to cytosolic ribosomal proteins, we were able to find 78 in the P. brasiliensis transcriptome. Nineteen of the 27 Saccharomyces cerevisiae genes related to translation initiation were also found. All eukaryotic elongation factors were detected in P. brasiliensis transcriptome, with eEF1A as one of the most expressed genes. Translation termination is performed, in eukaryotes, by factors 1 and 3 (eRF1, eRF3). In P. brasiliensis transcriptome it was possible to identify eRF3, but not eRF1. Sixteen PbAESTs showing aminoacyl-tRNA synthetase-predicted activities were found in our analyses, but no cysteinyl-, leucyl-, asparagyl- and arginyl-tRNA synthetases were detected. Among the mitochondrial ribosomal proteins, we have found 20 and 18 orthologs to S. cerevisiae large and small ribosomal subunit proteins, respectively. We have also found three PbAESTs similar to Neurospora crassa mitochondrial ribosomal genes, with no similarity with S. cerevisiae genes. Although orthologs to S. cerevisiae mitochondrial EF-Tu, EF-G and RF1 have been found in P. brasiliensis transcriptome, no sequences corresponding to functional EF-Ts were detected. In addition, 64 and 28 PbAESTs associated to protein modification and degradation, respectively, were found. These results suggest that these machineries are well conserved in P. brasiliensis, when compared to other organisms.