Proteomic analysis of early phosphorylated proteins in acute pancreatitis model

Background and Objective: The exact mechanism of acute pancreatitis (AP), which is an inflammation of the pancreas, still remains unclear. In this study, we examined the protein phosphorylation changes during the early stage of AP in mice using proteomic analysis. Methods: AP model in mice was constructed using an intraperitoneal injection of cerulein. Blood samples and pancreas were collected at 1, 3, 6, 9h after the final injection (n=3 at each time point). Samples collected 3h after the final injection were separately mixed and named S (saline group) and C1 (cerulein group); samples collected 6h after the final injection from the cerulein group were mixed and named C2. Proteins from S, C1, and C2 were extracted, digested by trypsin, and subjected to LC-MS/MS analysis, bioinformatics analysis, and Western blotting. Results: A total of 549 sites (426 proteins) were upregulated, and 501 sites (367 proteins) were downregulated in C1 compared to S; while 491 phosphorylation sites (377 proteins) were upregulated and 367 sites (274 proteins) were downregulated in C2 compared to S. Motif analysis showed that proline-directed kinase and basophilic kinase had a key role during early AP. During an early AP stage, the cellular distributions of proteins slightly changed. The types of domains changed with the development of AP. Phosphorylation proteins associated with calcium signaling, especially IP3R mediated calcium release, lysosome and autophagosome pathway, pancreatic digestive activation, and secretion, were found to be involved in the development of early AP independent of NF-kB activation. Moreover, the MAPK family was found to have a greater impact at the early stage of AP. We also found differentially expressed phosphorylations of amylase and trypsinogen and increased phosphorylation of MAPK6 S189 in early AP. Conclusion: IP3R mediated calcium release and activation of MAPK family are key events promoting the development of early AP.

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Three Biomarkers Identified From Serum Proteomic Analysis for the Detection of Early Stage Ovarian Cancer

Yearbook of Pathology and Laboratory Medicine ◽

10.1016/s1077-9108(08)70087-2 ◽

2006 ◽

Vol 2006 ◽

pp. 117-118

Author(s):

A.V. Parwani

Keyword(s):

Ovarian Cancer ◽

Proteomic Analysis ◽

Early Stage ◽

Early Stage Ovarian Cancer

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The factors for predicting hospital mortality in early stage of severe acute pancreatitis.

10.26226/morressier.59a6b342d462b80290b53fe3 ◽

2017 ◽

Author(s):

Masayasu Horibe

Keyword(s):

Acute Pancreatitis ◽

Hospital Mortality ◽

Severe Acute Pancreatitis ◽

Early Stage

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Genome-wide analysis of haloacid dehalogenase genes reveals their function in phosphate starvation responses in rice

PLoS ONE ◽

10.1371/journal.pone.0245600 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245600

Author(s):

Zezhen Du ◽

Suren Deng ◽

Zixuan Wu ◽

Chuang Wang

Keyword(s):

Bioinformatics Analysis ◽

Sequence Similarity ◽

Motif Analysis ◽

Systematic Classification ◽

Diverse Range ◽

Haloacid Dehalogenase ◽

Genome Wide ◽

Pi Starvation ◽

Had Superfamily ◽

Pi Stress

The HAD superfamily is named after the halogenated acid dehalogenase found in bacteria, which hydrolyses a diverse range of organic phosphate substrates. Although certain studies have shown the involvement of HAD genes in Pi starvation responses, systematic classification and bioinformatics analysis of the HAD superfamily in plants is lacking. In this study, 41 and 40 HAD genes were identified by genomic searching in rice and Arabidopsis, respectively. According to sequence similarity, these proteins are divided into three major groups and seven subgroups. Conserved motif analysis indicates that the majority of the identified HAD proteins contain phosphatase domains. A further structural analysis showed that HAD proteins have four conserved motifs and specified cap domains. Fewer HAD genes show collinearity relationships in both rice and Arabidopsis, which is consistent with the large variations in the HAD genes. Among the 41 HAD genes of rice, the promoters of 28 genes contain Pi-responsive cis-elements. Mining of transcriptome data and qRT-PCR results showed that at least the expression of 17 HAD genes was induced by Pi starvation in shoots or roots. These HAD proteins are predicted to be involved in intracellular or extracellular Po recycling under Pi stress conditions in plants.

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Plasma proteomic analysis of alcohol-induced acute pancreatitis by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)

Pancreatology ◽

10.1016/j.pan.2017.07.070 ◽

2017 ◽

Vol 17 (4) ◽

pp. S21

Author(s):

Byoung Kwan Son ◽

Aeeun Seok ◽

Hee-Gyoo Kang ◽

Jiyeong Lee ◽

Sora Mun ◽

...

Keyword(s):

Mass Spectrometry ◽

Acute Pancreatitis ◽

Liquid Chromatography ◽

Tandem Mass Spectrometry ◽

Proteomic Analysis ◽

Tandem Mass

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Urinary nitrogen excretion at the early stage of severe acute pancreatitis

Medical Science And Education Of Ural ◽

10.36361/1814-8999-2020-21-4-131-134 ◽

2020 ◽

Vol 21 (4) ◽

pp. 131-134

Author(s):

O. G. Sivkov ◽

◽

A. O. Sivkov ◽

Keyword(s):

Acute Pancreatitis ◽

Severe Acute Pancreatitis ◽

Early Stage ◽

Ideal Body Weight ◽

Nitrogen Excretion ◽

The Third ◽

Ideal Body ◽

Urinary Nitrogen Excretion ◽

Urinary Nitrogen ◽

The Ideal

Aim. To study urinary nitrogen excretion at the early stage of severe acute pancreatitis. Materials and methods. Prospective, single-center, cohort study. Inclusion criteria: diagnosis of acute pancreatitis and presence of at least one of the predictors of severe course. Among all patients (n = 72), a cohort of patients with severe acute pancreatitis (n = 32) was allocated. Three groups were formed in it: the first one – all patients, the second one – survivors (n = 24), the third one – deceased (n = 8). Urinary nitrogen excretion was determined using the Deacon formula. Measurements were performed on the first, third and fifth days of the disease. Statistical processing of the material was carried out by the SPSS software package. The null hypothesis was rejected at p < 0.05. Results. In the first week of the disease in all groups, the maximum urinary nitrogen excretion occurs on the 3rd day. When comparing the results of the second and third groups, it was found that the urinary nitrogen excretion on the first and fifth days did not have a statistically significant difference between the groups (respectively, p = 0.138, p = 0.572), and the results of the third day have (p = 0.014). A similar pattern remains when recalculating the nitrogen loss in the urine to the ideal weight; for the third day, the differences between the second and third groups were statistically significant (p = 0.007). ROC analysis of urinary nitrogen excretion of the third day calculated to the ideal body weight showed an area under the curve of 0.813 (p < 0.009). The value at the cut-off point is defined as 0.65 g/kg/day. The sensitivity of the model was 0.75%, specificity – 0.83%. Conclusion. If in a patient with acute pancreatitis, there is urinary nitrogen excretion on the third day from the onset of the disease, calculated to an ideal body weight of ≥ 0.65 g/kg/day, an unfavorable outcome of the disease is predicted.

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RNA and Oxidative Stress in Alzheimer’s Disease: Focus on microRNAs

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/2638130 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16

Author(s):

Akihiko Nunomura ◽

George Perry

Keyword(s):

Oxidative Stress ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Protein Misfolding ◽

Early Stage ◽

Brain Regions ◽

Prodromal Stage ◽

Adaptive Mechanisms ◽

Therapeutic Tools ◽

Key Events

Oxidative stress (OS) is one of the major pathomechanisms of Alzheimer’s disease (AD), which is closely associated with other key events in neurodegeneration such as mitochondrial dysfunction, inflammation, metal dysregulation, and protein misfolding. Oxidized RNAs are identified in brains of AD patients at the prodromal stage. Indeed, oxidized mRNA, rRNA, and tRNA lead to retarded or aberrant protein synthesis. OS interferes with not only these translational machineries but also regulatory mechanisms of noncoding RNAs, especially microRNAs (miRNAs). MiRNAs can be oxidized, which causes misrecognizing target mRNAs. Moreover, OS affects the expression of multiple miRNAs, and conversely, miRNAs regulate many genes involved in the OS response. Intriguingly, several miRNAs embedded in upstream regulators or downstream targets of OS are involved also in neurodegenerative pathways in AD. Specifically, seven upregulated miRNAs (miR-125b, miR-146a, miR-200c, miR-26b, miR-30e, miR-34a, miR-34c) and three downregulated miRNAs (miR-107, miR-210, miR-485), all of which are associated with OS, are found in vulnerable brain regions of AD at the prodromal stage. Growing evidence suggests that altered miRNAs may serve as targets for developing diagnostic or therapeutic tools for early-stage AD. Focusing on a neuroprotective transcriptional repressor, REST, and the concept of hormesis that are relevant to the OS response may provide clues to help us understand the role of the miRNA system in cellular and organismal adaptive mechanisms to OS.

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Effect of a New Cholecystokinin Receptor Antagonist (KSG 504) on the Early Stage of the Healing Process in Acute Pancreatitis Induced in Rats by the Closed Duodenal Loop Technique

Pancreas ◽

10.1097/00006676-199407000-00013 ◽

1994 ◽

Vol 9 (4) ◽

pp. 501-507 ◽

Cited By ~ 6

Author(s):

Sin-soo Ha ◽

Katsusuke Satake ◽

Akihito Hiura ◽

Michio Sowa ◽

Hideki Nishiwaki

Keyword(s):

Acute Pancreatitis ◽

Receptor Antagonist ◽

Early Stage ◽

Healing Process ◽

Cholecystokinin Receptor ◽

Closed Duodenal Loop ◽

Loop Technique

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Potential role of imaging for assessing acute pancreatitis-induced acute kidney injury

British Journal of Radiology ◽

10.1259/bjr.20200802 ◽

2020 ◽

pp. 20200802

Author(s):

Yi Wang ◽

Kaixiang Liu ◽

Xisheng Xie ◽

Bin Song

Keyword(s):

Acute Kidney Injury ◽

Acute Pancreatitis ◽

Early Stage ◽

Kidney Injury ◽

Current Evidence ◽

Advanced Imaging ◽

Creatinine Concentration ◽

New Techniques ◽

Magnetic Resonance Imaging Mri

Acute kidney injury (AKI) is a common complication of acute pancreatitis (AP) that is associated with increased mortality. Conventional assessment of AKI is based on changes in serum creatinine concentration and urinary output. However, these examinations have limited accuracy and sensitivity for the diagnosis of early-stage AKI. This review summarizes current evidence on the use of advanced imaging approaches and artificial intelligence (AI) for the early prediction and diagnosis of AKI in patients with AP. CT scores, CT post-processing technology, Doppler ultrasound, and AI technology provide increasingly valuable information for the diagnosis of AP-induced AKI. Magnetic resonance imaging (MRI) also has potential for the evaluation of AP-induced AKI. For the accurate diagnosis of early-stage AP-induced AKI, more studies are needed that use these new techniques and that use AI in combination with advanced imaging technologies.

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Label-Free Proteomics of the Fetal Pancreas Identifies Deficits in the Peroxisome in Rats with Intrauterine Growth Restriction

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/1520753 ◽

2019 ◽

Vol 2019 ◽

pp. 1-15

Author(s):

Xiaomei Liu ◽

Yanyan Guo ◽

Jun Wang ◽

Linlin Gao ◽

Caixia Liu

Keyword(s):

Oxidative Stress ◽

Cell Cycle ◽

Western Blotting ◽

Proteomic Analysis ◽

Intrauterine Growth Restriction ◽

Bioinformatics Analysis ◽

Growth Restriction ◽

Label Free ◽

Fetal Pancreas ◽

Intrauterine Growth

Aim. The objective of the present study was to identify differentially expressed proteins (DEPs) in the pancreas of a fetus with intrauterine growth restriction (IUGR) and to investigate the molecular mechanisms leading to adulthood diabetes in IUGR. Methods. The IUGR rat model was induced by maternal protein malnutrition. The fetal pancreas was collected at embryonic day 20 (E20). Protein was extracted, pooled, and subjected to label-free quantitative proteomic analysis. Bioinformatics analysis (GO and IPA) was performed to define the pathways and networks associated with DEPs. LC-MS results were confirmed by western blotting and/or quantitative PCR (q-PCR). The principal parameters of oxidative stress-superoxide dismutase (Sod) were determined in blood samples of fetal rats. Results. A total of 57 DEPs (27 upregulated, 30 downregulated) were identified with a 1.5-fold change threshold and a p value ≤ 0.05 between the IUGR and the control pancreas. Bioinformatics analysis revealed that these proteins play important roles in peroxisome biogenesis and fission, fatty acid beta-oxidation (FAO), mitotic cell cycle, and histone modification. The peroxin Pex14 was downregulated in the IUGR pancreas as confirmed by western blotting and q-PCR. Pmp70, a peroxisomal membrane protein involved in the transport of fatty acids, was upregulated. Hsd17b4 and Acox1/2, which catalyze different steps of peroxisomal FAO, were dysregulated. Sod plasma concentrations in the IUGR fetus were higher than those in the control, suggesting partial compensation for oxidative stress. Multiple DEPs were related to the regulation of the cell cycle, including reduced Cdk1, Mcm2, and Brd4. The histone acetylation regulators Hdac1/2 were downregulated, whereas Sirt1/3 and acetylated H3K56 were increased in the IUGR fetal pancreas. Conclusion. The present study identified DEPs in the fetal pancreas of IUGR rats by proteomic analysis. Downregulation of pancreas peroxins and dysregulation of enzymes involved in peroxisomal FAO may impair the biogenesis and function of the peroxisome and may underlie the development of T2 diabetes mellitus in adult IUGR rats. Disorders of cell cycle regulators may induce cell division arrest and lead to smaller islets. The present data provide new insight into the role of the peroxisome in the development of the pancreas and may be valuable in furthering our understanding of the pathogenesis of IUGR-induced diabetes.

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