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Multiple isoforms of Olive Flounder (Paralichthys olivaceus) Pax3a and Pax3b Display Differential Regulations on Myogenic Differentiation

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Journal of Ocean University of China 2022年第5期21卷 1295-1306页

作者： JIAO Shuang TAN Xungang YOU Feng PANG Qiuxiang Anti-Aging&Regenerative Medicine Research Institution School of Life Sciences and MedicineShandong University of TechnologyZibo 255000China Laboratory of Developmental and Evolutionary Biology School of Life Sciences and MedicineShandong University of TechnologyZibo 255000China CAS and Shandong Province Key Laboratory of Experimental Marine Biology Center for Ocean Mega-ScienceInstitute of OceanologyChinese Academy of SciencesQingdao 266071China Laboratory for Marine Biology and Biotechnology Pilot National Laboratory for Marine Science and Technology(Qingdao)Qingdao 266237China

Paired box 3(Pax3)is a critical upstream regulator of the onset of myogenesis.We have previously identified two spliced isoforms of pax3a(pax3a-1 and pax3a-2)and three spliced isoforms of pax3b(pax3b-1,pax3b-2,and pax3b-3)in olive flounder,but their roles in myogenesis are unknown.In this study,we investigated their cellular localization,transcriptional activity on myod gene regulation,and roles in myogenesis.Different Pax3a and Pax3b isoforms revealed various subcellular localizations,which were related to their corresponding protein structures.Pax3a-1,Pax3a-2,and Pax3b-1 promoted the transcriptional activity of myod to dif-ferent degrees,whereas Pax3b-2 and Pax3b-3 had a slight inhibitory or no effect.The pairwise interaction analysis demonstrated the synergistic effect of Pax3b-1 and Pax3b-3 on myod transcriptional activity.The overexpression of different pax3a and pax3b isoforms differentially altered the spatial expression patterns of myod and differentially regulated the expression levels of their target genes(myod,myf5,and c-met)in zebrafish embryonic myogenesis.In addition,the different flounder myod promoter-driven pax3a/3b isoform expression vectors were successfully introduced into the skeletal muscles of juvenile flounder by electroporation.How-ever,none of them could change the mRNA expression levels of mstn,myf5,myod,myogenin,pax7a,and pax7b in the electroporated muscles.These results suggest that different Pax3a and Pax3b isoforms may precisely and collaboratively regulate embryonic myogenesis,but their roles in juvenile myogenesis are uncertain.

关键词： Pax3a Pax3b isoforms myod myogenesis

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Aberrant expression of alternative isoforms of transcription factors in hepatocellular carcinoma

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World Journal of Hepatology 2018年第10期10卷 645-661页

作者： Olga Krivtsova Anna Makarova Natalia Lazarevich Federal State Budgetary Institution “N.N.Blokhin Medical Research Center of Oncology”of the Ministry of Health of the Russian FederationMoscow 115478Russian M.V.Lomonosov Moscow State University Moscow 119991Russian

Hepatocellular carcinoma(HCC) is one of the most prevalent malignancies worldwide and the second leading cause of death among all cancer types. Deregulation of the networks of tissue-specific transcription factors(TFs) observed in HCC leads to profound changes in the hepatic transcriptional program that facilitates tumor progression. In addition, recent reports suggest that substantial aberrations in the production of TF isoforms occur in HCC. In vitro experiments have identified distinct isoform-specific regulatory functions and related biological effects of liver-specific TFs that are implicated in carcinogenesis, which may be relevant for tumor progression and clinical outcome. This study reviews available data on the expression of isoforms of liver-specific and ubiquitous TFs in the liver and HCC and their effects, including HNF4α, C/EBPs, p73 and TCF7 L2, and indicates that assessment of the ratio of isoforms and targeting specific TF variants may be beneficial for the prognosis and treatment of HCC.

关键词： Alternative isoforms Transcription factors Hepatocellular carcinoma Alternative splicing Hepatic differentiation Personalized treatment

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Androgen receptor isoforms in human and rat prostate

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Asian Journal of Andrology 2000年第4期2卷 307-310页

作者： Shu-JieXIA Gang-YaoHAO Xiao-DaTANG UniversityDepartmentofUrology ShanghaiFirstPeople＇sHospitalFudanUniversityShanghai200080China DepartmentofUrology SecondAffiliatedHospitalShandongUniversityJinan250033China UniversityDepartmentofUrology ShanghaiFirstPeople＇sHospitalFudanUniversityShanghai200080China

Aim: To investigate the androgen receptor (AR) isoforms and its variability of expression in human and rat prostatictissues. Methods: Human benign prostatic hyperplasia (BPH) and prostatic cancer tissues were obtained from pa-tients undergoing prostatectomy, and rat ventral prostate was incised 3 days after castration. Forty-one AR-positive BPHspecimens, 3 prostatic cancer specimens, and 6 rat prostates were used. After processing at 4℃, the tissues were ex-amined by means of high resolution isoelectric focusing (IEF) technique to determine their AR isoforms. Results:From the prostatic specimens, 3 types of AR isoforms were detected with pI values at 6.5, 6.0, and 5.3. In humanBPH tissues, 15/41 (36.6%) specimens showed all the three types of isoforms, while 19/41 (46.3%) showed 2 iso-fora at various combinations and 7/41 (17.1%), 1 isoform. For the 3 prostatic cancer specimens, one showed 3 iso-forms, one, 2 isoforms, and the other failed to show any isoform. All rat prostatic tissues showed 2 isoforms at differ-ent combinations. Binding of ~3H-dihydrotestosterone (DHT) to the isoforms was inhibited by the addition of 100-foldexcess of DHT or testosterone, but not progesterone, oestradiol or diethylstilboestrol. Conclusion: AR isoforms aredifferent in different patients. Although their genesis is not clear, the therapeutic implication of the present observationappears to be interesting, that may help clarifying the individual differences in the response to hormonal therapy.(Asian J Androl 2000 Dec; 2: 307-310)

关键词： androgen receptors isoforms prostate

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Bucolome N-Glucuronide Formation: Species Differences and Identification of Human UDP-Glucuronosyltransferase isoforms

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Pharmacology & Pharmacy 2011年第4期2卷 361-369页

作者： Humihisa Kanoh Makiko Tada Yoshihiro Uesawa Kiminori Mohri 不详

The barbituric acid derivative bucolome (BCP) is a nonsteroidal anti-inflammatory drug. The present study investigated whether BCP N-glucuronide (BCP-NG, the primary metabolite of BCP) was produced in mammalian species other than rats, and attempted to identify the UDP-glucuronosyltransferase (UGT) isoform (s) responsible for formation of BCP-NG in humans. BCP-NG was detected in all species tested. The results were as follows (pmol equivalent/ min/mg protein): rat, 479 ± 83;Mongolian gerbil, 378 ± 9;rabbit, 275 ±26;guinea pig, 257 ± 10;human, 242 ± 18;hamster, 177 ± 22;and mouse, 167 ± 15. Since human liver microsomes formed BCP-NG, we investigated the metabolites of BCP excreted in the urine of a patient after oral administration of BCP (600 mg). BCP and BCP-NG were excreted in the urine at amounts of 2.9 mg (about 0.5% of the dose) and 14.4 mg (about 2.5% of the dose) over 12 hours. In order to identify the UGT isoforms involved in formation of BCP-NG in humans, we investigated BCP-NG formation by the microsomes of insect cells expressing each of twelve UGT isoforms (hUGT1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B4, 2B7, 2B15, and 2B17). As a result, BCP-NG formation (pmol equivalents/min/mg protein) was observed with microsomes expressing hUGT1A1 (142), 1A3 (196), 1A4 (8), 1A7 (8), 1A8 (66), 1A9 (38), 1A10 (9), 2B4 (7) and 2B7 (16). In particular, the activity of hUGT1A1 and 1A3 was high. These results suggest that the UGT isoforms responsible for formation of BCP-NG exist in various mammalian species, including humans, and that the UGT 1A family is primarily responsible for BCP N-glucuronide formation in humans.

关键词： Bucolome Bucolome N-Glucuronide UGT isoforms Barbiturate Barbiturate N-Glucuronide

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A robust test for growth hormone doping- present status and future prospects

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Asian Journal of Andrology 2008年第3期10卷 416-425页

作者： Anne E. Nelson Ken K. Ho Pituitary Research Unit Garvan Institute of Medical Research Darlinghurst NSW 2010 Australia

Although doping with growth hormone （GH） is banned, there is anecdotal evidence that it is widely abused. GH is reportedly used often in combination with anabolic steroids at high doses for several months. Development of a robust test for GH has been challenging because recombinant human 22 kDa （22K） GH used in doping is indistinguishable analytically from endogenous GH and there are wide physiological fluctuations in circulating GH concentrations. One approach to GH testing is based on measurement of different circulating GH isoforms using immunoassays that differentiate between 22K and other GH isoforms. Administration of 22K GH results in a change in its abundance relative to other endogenous pituitary GH isoforms. The differential isoform method has been implemented; however, its utility is limited because of the short window of opportunity of detection. The second approach, which will extend the window of opportunity of detection, is based on the detection of increased levels of circulating GH-responsive proteins, such as insulin-like growth factor （IGF） axis and collagen peptides. Age and gender are the major determinants of variability for IGF-I and the collagen markers; therefore, a test based on these markers must take age into account for men and women. Extensive data is now available that validates the GH- responsive marker approach and implementation is now largely dependent on establishing an assured supply of standardized assays. Future directions will include more widespread implementation of both approaches by the World Anti-Doping Agency, possible use of other platforms for measurement and an athlete＇s passport to establish individual reference levels for biological parameters such as GH-responsive markers. Novel approaches include gene expression and proteomic profiling.

关键词： growth hormone doping athletes isoforms growth hormone-responsive markers

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Mass spectrometry based proteomics,background,status and future needs

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Protein & Cell 2012年第9期3卷 641-647页

作者： Peter Roepstorff Department of Biochemistry and Molecular Biology University of Southern Denmark Campusvej 55DK 5230 Odense MDenmark

An overview of the background for proteomics and a description of the present state of art are given with a description of the main strategies in proteomics.The advantages and limitations of the two major strategies,2D-gel based and LC-MS based,are discussed and a combination for the two,CeLC-MS is described.A number of challenging problems which have been solved using different proteomics strategies including the advantage of organell enrichment or modifications specific peptide isolation to get deeper into the proteome are described.Finally the present status and future needs discussed.

关键词： proteomics 2D-PAGE LC-MS isoforms phosphorylation

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PsyMuKB: An Integrative De Novo Variant Knowledge Base for Developmental Disorders

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Genomics, Proteomics & Bioinformatics 2019年第4期17卷 453-464页

作者： Guan Ning Lin Sijia Guo Xian Tan Weidi Wang Wei Qian Weichen Song Jingru Wang Shunying Yu Zhen Wang Donghong Cui Han Wang Shanghai Mental Health Center Shanghai Jiao Tong University School of MedicineSchool of Biomedical EngineeringShanghai Jiao Tong UniversityShanghai 200030China Shanghai Key Laboratory of Psychotic Disorders Shanghai 200030China Brain Science and Technology Research Center Shanghai Jiao Tong UniversityShanghai 200030China College of Information Science and Technology Northeast Normal UniversityChangchun 130117China Institution of Computational Biology Northeast Normal UniversityChangchun 130117China

De novo variants(DNVs)are one of the most significant contributors to severe earlyonset genetic disorders such as autism spectrum disorder,intellectual disability,and other developmental and neuropsychiatric(DNP)disorders.Presently,a plethora of DNVs have been identified using next-generation sequencing,and many efforts have been made to understand their impact at the gene level.However,there has been little exploration of the effects at the isoform level.The brain contains a high level of alternative splicing and regulation,and exhibits a more divergent splicing program than other tissues.Therefore,it is crucial to explore variants at the transcriptional regulation level to better interpret the mechanisms underlying DNP disorders.To facilitate a better usage and improve the isoform-level interpretation of variants,we developed NeuroPsychiatric Mutation Knowledge Base(PsyMuKB).It contains a comprehensive,carefully curated list of DNVs with transcriptional and translational annotations to enable identification of isoformspecific mutations.PsyMuKB allows a flexible search of genes or variants and provides both table-based descriptions and associated visualizations,such as expression,transcript genomic structures,protein interactions,and the mutation sites mapped on the protein structures.It also provides an easy-to-use web interface,allowing users to rapidly visualize the locations and characteristics of mutations and the expression patterns of the impacted genes and isoforms.PsyMuKB thus constitutes a valuable resource for identifying tissue-specific DNVs for further functional studies of related disorders.PsyMuKB is freely accessible at http://***.

关键词： De novo mutation Developmental and neuropsychiatric disorders Database isoforms Tissue specificity

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DNA Methylation Affects Gene Alternative Splicing in Plants： An Example from Rice

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Molecular Plant 2016年第2期9卷 305-307页

作者： Wang, Xutong Hu, Lanjuan Wang, Xiaofei Li, Ning Xu, Chunming Gong, Lei Liu, Bao NE Normal Univ Key Lab Mol Epigenet Minist Educ MOE Changchun 130024 Peoples R China

Dear Editor,Alternative splicing （AS） of pre-mRNA is an evolutionarily conserved mechanism to increase transcriptomic and proteomic complexity, and hence phenotypic diversity, via the production of multiple mRNA isoforms from a single gene （Reddy et al., 2013）. AS is regulated by various cis-acting regulatory elements and RNA-binding proteins （Reddy et al., 2013）.

关键词： complexity isoforms various

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DNA vaccine and asthma therapy

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Chinese Medical Journal 2005年第7期118卷 531-533页

作者： SHIHuan-zhong DepartmentsofRespiratoryandCriticalCareMedicine FirstAffiliatedHospitalGuangxiMedicalUniversityNanning530021China

Allergic asthma is currently considered a chronic airway inflammatory disorder associated with the presence of activated CD_4^+ Th2-type lymphocytes, eosinophils, and mast cells. Interestingly, therapeutic strategies based on immune deviation and suppression have been shown to successfully attenuate the development of the asthma phenotype. Despite the clear rational for immunotherapy, the usefulness of this approach has been limited by the potential for adverse effects, particularly anaphylaxis, and the relatively crude nature of the allergen extracts that are available. To overcome these problems, revised strategies have been assessed in animals

关键词： HOUSE-DUST-MITE ALLERGEN IMMUNOTHERAPY POLLEN IMMUNIZATION MECHANISM isoforms ALPHA

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Cell signaling associated with internalization of 67 kDa laminin receptor (67LR) by soluble laminin and its implication for protection against neurodegenerative diseases

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Neural Regeneration Research 2019年第9期14卷 1513-1514页

作者： Rayudu Gopalakrishna Narayan R.Bhat Sarah Zhou William J.Mack Department of Integrative Anatomical Sciences Keck School of MedicineLos AngelesCAUSA Department of Neurological Surgery Keck School of MedicineLos AngelesCAUSA Department of Neuroscience Medical University of South CarolinaCharlestonSCUSA

Various isoforms of laminins are present in the basement membranes complexed with other structural proteins.In the central nervous system(CNS),they are primarily localized to the basement membranes of blood vessels and reactive astrocytes.Limited amounts of various laminin isoforms are also associated with neuronal cell bodies and axons,which are referred to as“neuronal”laminins(Yamamoto et al.,1988).They exist in a soluble form,free from other basement membrane proteins.Neurons either produce these soluble laminins or acquire them from astroglial cells.Laminin stimulates neuritogenesis and confers neuroprotection in vitro,but their exact role of these neuronal soluble laminins in the CNS is yet unknown.

关键词： Various isoforms basement membranes confers neuroprotection

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