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Article ; Online: In Vitro Effects of Emerging Bisphenols on Myocyte Differentiation and Insulin Responsiveness.

Jing, Jiongjie / Pu, Yong / Veiga-Lopez, Almudena / Lyu, Lihua

Toxicological sciences : an official journal of the Society of Toxicology

2021 Volume 178, Issue 1, Page(s) 189–200

Abstract: Bisphenols are endocrine disrupting chemicals to which humans are ubiquitously exposed to. Prenatal bisphenol A exposure can lead to insulin resistance. However, the metabolic effects of other emerging bisphenols, such as bisphenol S (BPS) and bisphenol ... ...

Abstract	Bisphenols are endocrine disrupting chemicals to which humans are ubiquitously exposed to. Prenatal bisphenol A exposure can lead to insulin resistance. However, the metabolic effects of other emerging bisphenols, such as bisphenol S (BPS) and bisphenol F (BPF), are less understood. Because the skeletal muscle is the largest of the insulin target tissues, the goal of this study was to evaluate the effects of 2 emerging bisphenols (BPS and BPF) on cytotoxicity, proliferation, myogenic differentiation, and insulin responsiveness in skeletal muscle cells. We tested this using a dose-response approach in C2C12 mouse and L6 rat myoblast cell lines. The results showed that C2C12 mouse myoblasts were more susceptible to bisphenols compared with L6 rat myoblasts. In both cell lines, bisphenol A was more cytotoxic, followed by BPF and BPS. C2C12 myoblast proliferation was higher upon BPF exposure at the 10-4 M dose and the fusion index was increased after exposure to either BPF or BPS at doses over 10-10 M. Exposure to BPS and BPF also reduced baseline expression of p-AKT (Thr) and p-GSK-3β, but not downstream effectors such as mTOR and glucose transporter-4. In conclusion, at noncytotoxic doses, BPS and BPF can alter myoblast cell proliferation, differentiation, and partially modulate early effectors of the insulin receptor signaling pathway. However, BPS or BPF short-term exposure evaluated here does not result in impaired insulin responsiveness.
MeSH term(s)	Animals ; Benzhydryl Compounds/toxicity ; Cell Differentiation/drug effects ; Cell Line ; Glycogen Synthase Kinase 3 beta ; Insulin ; Mice ; Muscle Cells/drug effects ; Phenols/toxicity ; Rats ; Receptor, Insulin/metabolism ; Signal Transduction
Chemical Substances	Benzhydryl Compounds ; Insulin ; Phenols ; Receptor, Insulin (EC 2.7.10.1) ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; bisphenol A (MLT3645I99)
Language	English
Publishing date	2021-05-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1420885-4
ISSN	1096-0929 ; 1096-6080
ISSN (online)	1096-0929
ISSN	1096-6080
DOI	10.1093/toxsci/kfaa130
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Article ; Online: Identification and validation of key biomarkers based on RNA methylation genes in sepsis.

Zhang, Qianqian / Bao, Xiaowei / Cui, Mintian / Wang, Chunxue / Ji, Jinlu / Jing, Jiongjie / Zhou, Xiaohui / Chen, Kun / Tang, Lunxian

Frontiers in immunology

2023 Volume 14, Page(s) 1231898

Abstract: Background: RNA methylation is closely involved in immune regulation, but its role in sepsis remains unknown. Here, we aim to investigate the role of RNA methylation-associated genes (RMGs) in classifying and diagnosing of sepsis.: Methods: Five ... ...

Abstract	Background: RNA methylation is closely involved in immune regulation, but its role in sepsis remains unknown. Here, we aim to investigate the role of RNA methylation-associated genes (RMGs) in classifying and diagnosing of sepsis. Methods: Five types of RMGs (m1A, m5C, m6Am, m7G and Ψ) were used to identify sepsis subgroups based on gene expression profile data obtained from the GEO database (GSE57065, GSE65682, and GSE95233). Unsupervised clustering analysis was used to identify distinct RNA modification subtypes. The CIBERSORT, WGCNA, GO and KEGG analysis were performed to explore immune infiltration pattern and biological function of each cluster. RF, SVM, XGB, and GLM algorithm were applied to identify the diagnostic RMGs in sepsis. Finally, the expression levels of the five key RMGs were verified by collecting PBMCs from septic patients using qRT-PCR, and their diagnostic efficacy for sepsis was verified in combination with clinical data using ROC analysis. Results: Sepsis was divided into three subtypes (cluster 1 to 3). Cluster 1 highly expressed Conclusions: Our study uncovered that dysregulation of RNA methylation genes (m1A, m5C, m6Am, m7G and Ψ) was closely involved in the pathogenesis of sepsis, providing new insights into the classification of sepsis endotypes. We also revealed that five hub RMGs could function as novel diagnostic biomarkers and potential targets for treatment.
MeSH term(s)	Humans ; Methylation ; Sepsis/diagnosis ; Sepsis/genetics ; Algorithms ; Biomarkers ; RNA ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO ; tRNA Methyltransferases
Chemical Substances	Biomarkers ; RNA (63231-63-0) ; FTO protein, human (EC 1.14.11.33) ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO (EC 1.14.11.33) ; NSUN6 protein, human (EC 2.1.1.-) ; tRNA Methyltransferases (EC 2.1.1.-)
Language	English
Publishing date	2023-08-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1231898
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Article ; Online: Deciphering the molecular and cellular atlas of immune cells in septic patients with different bacterial infections.

Sun, Ping / Cui, Mintian / Jing, Jiongjie / Kong, Fanyu / Wang, Shixi / Tang, Lunxian / Leng, Junling / Chen, Kun

Journal of translational medicine

2023 Volume 21, Issue 1, Page(s) 777

Abstract: Background: Sepsis is a life-threatening organ dysfunction caused by abnormal immune responses to various, predominantly bacterial, infections. Different bacterial infections lead to substantial variation in disease manifestation and therapeutic ... ...

Abstract	Background: Sepsis is a life-threatening organ dysfunction caused by abnormal immune responses to various, predominantly bacterial, infections. Different bacterial infections lead to substantial variation in disease manifestation and therapeutic strategies. However, the underlying cellular heterogeneity and mechanisms involved remain poorly understood. Methods: Multiple bulk transcriptome datasets from septic patients with 12 types of bacterial infections were integrated to identify signature genes for each infection. Signature genes were mapped onto an integrated large single-cell RNA (scRNA) dataset from septic patients, to identify subsets of cells associated with different sepsis types, and multiple omics datasets were combined to reveal the underlying molecular mechanisms. In addition, an scRNA dataset and spatial transcriptome data were used to identify signaling pathways in sepsis-related cells. Finally, molecular screening, optimization, and de novo design were conducted to identify potential targeted drugs and compounds. Results: We elucidated the cellular heterogeneity among septic patients with different bacterial infections. In Escherichia coli (E. coli) sepsis, 19 signature genes involved in epigenetic regulation and metabolism were identified, of which DRAM1 was demonstrated to promote autophagy and glycolysis in response to E. coli infection. DRAM1 upregulation was confirmed in an independent sepsis cohort. Further, we showed that DRAM1 could maintain survival of a pro-inflammatory monocyte subset, C10_ULK1, which induces systemic inflammation by interacting with other cell subsets via resistin and integrin signaling pathways in blood and kidney tissue, respectively. Finally, retapamulin was identified and optimized as a potential drug for treatment of E. coli sepsis targeting the signature gene, DRAM1, and inhibiting E. coli protein synthesis. Several other targeted drugs were also identified in other types of sepsis, including nystatin targeting C1QA in Neisseria sepsis and dalfopristin targeting CTSD in Streptococcus viridans sepsis. Conclusion: Our study provides a comprehensive overview of the cellular heterogeneity and underlying mechanisms in septic patients with various bacterial infections, providing insights to inform development of stratified targeted therapies for sepsis.
MeSH term(s)	Humans ; Escherichia coli ; Epigenesis, Genetic ; Bacterial Infections/genetics ; Sepsis/genetics ; Sepsis/microbiology ; Transcriptome
Language	English
Publishing date	2023-11-02
Publishing country	England
Document type	Review ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2118570-0
ISSN	1479-5876 ; 1479-5876
ISSN (online)	1479-5876
ISSN	1479-5876
DOI	10.1186/s12967-023-04631-4
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Article: Cross-talk between NOTCH2 and BMP4/SMAD signaling pathways in bovine follicular granulosa cells

Li, Yating / Jing, Jiongjie / Dang, Wenqing / Jia, Kaiqi / Guo, Xiangyu / Kebreab, Ermias / Lyu, Lihua / Zhao, Junxing

Theriogenology. 2022 Apr. 20,

2022

Abstract: NOTCH and bone morphogenetic protein (BMP)/SMAD signaling play key regulatory roles in mammalian ovarian development. The study aimed to investigate interregulatory mechanisms between NOTCH2 and BMP4/SMAD signaling pathways in bovine follicular granulosa ...

Abstract	NOTCH and bone morphogenetic protein (BMP)/SMAD signaling play key regulatory roles in mammalian ovarian development. The study aimed to investigate interregulatory mechanisms between NOTCH2 and BMP4/SMAD signaling pathways in bovine follicular granulosa cells (GCs). The results showed that NOTCH2 silence reduced the mRNA expression of SMAD1, SMAD5, SMAD8 (also known as SMAD9) and Mg²⁺/Mn²⁺- dependent Protein Phosphatase 1A (PPM1A), which are effectors of BMP/SMAD signaling pathway (P < 0.01). Overexpressing NOTCH2 intracellular sequence increased the mRNA expression of BMPR1A, SMAD1, SMAD4, SMAD5, SMAD8 and PPM1A (P < 0.01). Meanwhile, treating GCs with BMP4 inhibited the mRNA expression of its downstream gene SMAD1 and steroidogenesis genes STAR and CYP11A1 in the presence of follicular stimulating hormone (FSH) (P < 0.01). Moreover, BMP4 inhibited the mRNA expression of NOTCH signaling pathway target gene HES1 (P < 0.05), while the increase in NOTCH2 may be due to negative feedback of HES1. By and large, these results indicated that NOTCH2 up-regulated key genes of BMP/SMAD signaling in bovine follicle GCs, while BMP4 inhibited its downstream signaling factors and NOTCH signaling pathway target gene HES1. This study suggests there are complex synergistic and antagonistic effects between the two signaling pathways, which jointly participate in regulating bovine follicular development through regulating follicular GCs.
Keywords	animal reproduction ; bone morphogenetic proteins ; cattle ; follicular development ; genes ; steroidogenesis
Language	English
Dates of publication	2022-0420
Publishing place	Elsevier Inc.
Document type	Article
Note	Pre-press version
ZDB-ID	189232-0
ISSN	1879-3231 ; 0093-691X
ISSN (online)	1879-3231
ISSN	0093-691X
DOI	10.1016/j.theriogenology.2022.04.016
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Article ; Online: Expression of ABC transporters during syncytialization in preeclampsia.

Sethuraman, Visalakshi / Pu, Yong / Gingrich, Jeremy / Jing, Jiongjie / Long, Robert / Olomu, Isoken Nicholas / Veiga-Lopez, Almudena

Pregnancy hypertension

2022 Volume 27, Page(s) 181–188

Abstract: Preeclampsia complicates 2-8% of pregnancies and is associated with prematurity and intrauterine growth restriction. Cholesterol and sterol transport is a key function of the placenta and it is elicited through ATP binding cassette (ABC) transporters. ... ...

Abstract	Preeclampsia complicates 2-8% of pregnancies and is associated with prematurity and intrauterine growth restriction. Cholesterol and sterol transport is a key function of the placenta and it is elicited through ATP binding cassette (ABC) transporters. ABCA1 expression changes during trophoblast cell fusion, a process required to form the placental syncytium that enables maternal-fetal nutrient transfer. ABCA1 expression is dysregulated in preeclamptic placentas. But whether ABC transporters expression during trophoblast fusion is disrupted in preeclampsia remains unknown. We investigated if cholesterol and sterol ABC transporters are altered in term and preterm preeclampsia placentas and during human cytotrophoblast syncytialization. Human placental biopsies were collected from healthy term (≥37 weeks; n = 11) and term preeclamptic (≥36 6/7 weeks; n = 8) and pre-term preeclamptic (28-35 weeks; n = 8) pregnancies. Both, protein and mRNA expression for ABCA1, ABCG1, ABCG5, and ABCG8 were evaluated. Primary cytotrophoblasts isolated from a subset of placentas were induced to syncytialize for 96 h and ABCA1, ABCG1 and ABCG8 mRNA expression evaluated at 0 h and 96 h. Protein and gene expression of ABC transporters were not altered in preeclamptic placentas. In the healthy Term group, ABCA1 expression was similar before and after syncytialization. After 96 h of syncytialization, mRNA expression of ABCA1 and ABCG1 increased significantly, while ABCG8 decreased significantly in term-preeclampsia, but not pre-term preeclampsia. While placental expression of ABCA1 and ABCG1 remained unaltered in term preeclampsia, the disruption in their dynamic expression pattern during cytotrophoblast syncytialization suggests that cholesterol transport may contribute to the pathophysiologic role of the placenta in preeclampsia.
MeSH term(s)	ATP Binding Cassette Transporter 1/genetics ; ATP Binding Cassette Transporter 1/metabolism ; ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics ; ATP Binding Cassette Transporter, Subfamily G, Member 1/metabolism ; Adult ; Case-Control Studies ; Cholesterol/metabolism ; Female ; Gene Expression Regulation, Developmental ; Humans ; Infant, Newborn ; Male ; Placenta/metabolism ; Pre-Eclampsia/genetics ; Pregnancy ; RNA, Messenger/metabolism
Chemical Substances	ABCA1 protein, human ; ABCG1 protein, human ; ATP Binding Cassette Transporter 1 ; ATP Binding Cassette Transporter, Subfamily G, Member 1 ; RNA, Messenger ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2022-01-31
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2584464-7
ISSN	2210-7797 ; 2210-7789
ISSN (online)	2210-7797
ISSN	2210-7789
DOI	10.1016/j.preghy.2022.01.006
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Article ; Online: Cross-talk between NOTCH2 and BMP4/SMAD signaling pathways in bovine follicular granulosa cells.

Li, Yating / Jing, Jiongjie / Dang, Wenqing / Jia, Kaiqi / Guo, Xiangyu / Kebreab, Ermias / Lyu, Lihua / Zhao, Junxing

Theriogenology

2022 Volume 187, Page(s) 74–81

Abstract	NOTCH and bone morphogenetic protein (BMP)/SMAD signaling play key regulatory roles in mammalian ovarian development. The study aimed to investigate interregulatory mechanisms between NOTCH2 and BMP4/SMAD signaling pathways in bovine follicular granulosa cells (GCs). The results showed that NOTCH2 silence reduced the mRNA expression of SMAD1, SMAD5, SMAD8 (also known as SMAD9) and Mg
MeSH term(s)	Animals ; Cattle ; Cells, Cultured ; Female ; Follicle Stimulating Hormone/pharmacology ; Granulosa Cells/physiology ; Mammals ; Phosphoprotein Phosphatases ; RNA, Messenger/metabolism ; Signal Transduction/physiology
Chemical Substances	RNA, Messenger ; Follicle Stimulating Hormone (9002-68-0) ; Phosphoprotein Phosphatases (EC 3.1.3.16)
Language	English
Publishing date	2022-04-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	189232-0
ISSN	1879-3231 ; 0093-691X
ISSN (online)	1879-3231
ISSN	0093-691X
DOI	10.1016/j.theriogenology.2022.04.016
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Article ; Online: Gestational Exposure to Bisphenol A and Bisphenol S Leads to Fetal Skeletal Muscle Hypertrophy Independent of Sex.

Jing, Jiongjie / Pu, Yong / Gingrich, Jeremy / Veiga-Lopez, Almudena

Toxicological sciences : an official journal of the Society of Toxicology

2019 Volume 172, Issue 2, Page(s) 292–302

Abstract: Gestational exposure to bisphenol A (BPA) can lead to offspring insulin resistance. However, despite the role that the skeletal muscle plays in glucose homeostasis, it remains unknown whether gestational exposure to BPA, or its analog bisphenol S (BPS), ... ...

Abstract	Gestational exposure to bisphenol A (BPA) can lead to offspring insulin resistance. However, despite the role that the skeletal muscle plays in glucose homeostasis, it remains unknown whether gestational exposure to BPA, or its analog bisphenol S (BPS), impairs skeletal muscle development. We hypothesized that gestational exposure to BPA or BPS will impair fetal muscle development and lead to muscle-specific insulin resistance. To test this, pregnant sheep (n = 7-8/group) were exposed to BPA or BPS from gestational day (GD) 30 to 100. At GD120, fetal skeletal muscle was harvested to evaluate fiber size, fiber type, and gene and protein expression related to myogenesis, fiber size, fiber type, and inflammation. Fetal primary myoblasts were isolated to evaluate proliferation and differentiation. In fetal skeletal muscle, myofibers were larger in BPA and BPS groups in both females and males. BPA females had higher MYH1 (reflective of type-IIX fast glycolytic fibers), whereas BPS females had higher MYH2 and MYH7, and higher myogenic regulatory factors (Myf5, MyoG, MyoD, and MRF4) mRNA expression. No differences were observed in males. Myoblast proliferation was not altered in gestationally BPA- or BPS-exposed myoblasts, but upon differentiation, area and diameter of myotubes were larger independent of sex. Females had larger myofibers and myotubes than males in all treatment groups. In conclusion, gestational exposure to BPA or BPS does not result in insulin resistance in fetal myoblasts but leads to fetal fiber hypertrophy in skeletal muscle independent of sex and alters fiber type distribution in a sex-specific manner.
MeSH term(s)	Animals ; Benzhydryl Compounds/blood ; Benzhydryl Compounds/toxicity ; Cell Differentiation/drug effects ; Cell Proliferation/drug effects ; Cells, Cultured ; Endocrine Disruptors/blood ; Endocrine Disruptors/toxicity ; Female ; Fetal Development/drug effects ; Gestational Age ; Hypertrophy ; Muscle Cells/drug effects ; Muscle Cells/pathology ; Muscle Development/drug effects ; Muscle, Skeletal/drug effects ; Muscle, Skeletal/embryology ; Muscle, Skeletal/pathology ; Myoblasts/drug effects ; Myoblasts/pathology ; Phenols/blood ; Phenols/toxicity ; Pregnancy ; Prenatal Exposure Delayed Effects/chemically induced ; Prenatal Exposure Delayed Effects/pathology ; Primary Cell Culture ; Sheep ; Sulfones/blood ; Sulfones/toxicity
Chemical Substances	Benzhydryl Compounds ; Endocrine Disruptors ; Phenols ; Sulfones ; bis(4-hydroxyphenyl)sulfone (80-09-1) ; bisphenol A (MLT3645I99)
Language	English
Publishing date	2019-09-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1420885-4
ISSN	1096-0929 ; 1096-6080
ISSN (online)	1096-0929
ISSN	1096-6080
DOI	10.1093/toxsci/kfz198
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Article ; Online: piRNA loading triggers MIWI translocation from the intermitochondrial cement to chromatoid body during mouse spermatogenesis.

Wei, Huan / Gao, Jie / Lin, Di-Hang / Geng, Ruirong / Liao, Jiaoyang / Huang, Tian-Yu / Shang, Guanyi / Jing, Jiongjie / Fan, Zong-Wei / Pan, Duo / Yin, Zi-Qi / Li, Tianming / Liu, Xinyu / Zhao, Shuang / Chen, Chen / Li, Jinsong / Wang, Xin / Ding, Deqiang / Liu, Mo-Fang

Nature communications

2024 Volume 15, Issue 1, Page(s) 2343

Abstract: The intermitochondrial cement (IMC) and chromatoid body (CB) are posited as central sites for piRNA activity in mice, with MIWI initially assembling in the IMC for piRNA processing before translocating to the CB for functional deployment. The regulatory ... ...

Abstract	The intermitochondrial cement (IMC) and chromatoid body (CB) are posited as central sites for piRNA activity in mice, with MIWI initially assembling in the IMC for piRNA processing before translocating to the CB for functional deployment. The regulatory mechanism underpinning MIWI translocation, however, has remained elusive. We unveil that piRNA loading is the trigger for MIWI translocation from the IMC to CB. Mechanistically, piRNA loading facilitates MIWI release from the IMC by weakening its ties with the mitochondria-anchored TDRKH. This, in turn, enables arginine methylation of MIWI, augmenting its binding affinity for TDRD6 and ensuring its integration within the CB. Notably, loss of piRNA-loading ability causes MIWI entrapment in the IMC and its destabilization in male germ cells, leading to defective spermatogenesis and male infertility in mice. Collectively, our findings establish the critical role of piRNA loading in MIWI translocation during spermatogenesis, offering new insights into piRNA biology in mammals.
MeSH term(s)	Animals ; Male ; Mice ; Argonaute Proteins/metabolism ; Germ Cell Ribonucleoprotein Granules ; Germ Cells/metabolism ; Mammals/genetics ; Mitochondria/metabolism ; Piwi-Interacting RNA ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Spermatogenesis/genetics ; Testis/metabolism
Chemical Substances	Argonaute Proteins ; Piwi-Interacting RNA ; RNA, Small Interfering ; Piwil1 protein, mouse
Language	English
Publishing date	2024-03-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-46664-3
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Article ; Online: MIWI N-terminal RG motif promotes efficient pachytene piRNA production and spermatogenesis independent of LINE1 transposon silencing.

Wei, Chao / Jing, Jiongjie / Yan, Xiaoyuan / Mann, Jeffrey M / Geng, Ruirong / Xie, Huirong / Demireva, Elena Y / Hess, Rex A / Ding, Deqiang / Chen, Chen

PLoS genetics

2023 Volume 19, Issue 11, Page(s) e1011031

Abstract: PIWI proteins and their associated piRNAs act to silence transposons and promote gametogenesis. Murine PIWI proteins MIWI, MILI, and MIWI2 have multiple arginine and glycine (RG)-rich motifs at their N-terminal domains. Despite being known as docking ... ...

Abstract	PIWI proteins and their associated piRNAs act to silence transposons and promote gametogenesis. Murine PIWI proteins MIWI, MILI, and MIWI2 have multiple arginine and glycine (RG)-rich motifs at their N-terminal domains. Despite being known as docking sites for the TDRD family proteins, the in vivo regulatory roles for these RG motifs in directing PIWI in piRNA biogenesis and spermatogenesis remain elusive. To investigate the functional significance of RG motifs in mammalian PIWI proteins in vivo, we genetically engineered an arginine to lysine (RK) point mutation of a conserved N-terminal RG motif in MIWI in mice. We show that this tiny MIWI RG motif is indispensable for piRNA biogenesis and male fertility. The RK mutation in the RG motif disrupts MIWI-TDRKH interaction and impairs enrichment of MIWI to the intermitochondrial cement (IMC) for efficient piRNA production. Despite significant overall piRNA level reduction, piRNA trimming and maturation are not affected by the RK mutation. Consequently, MiwiRK mutant mice show chromatoid body malformation, spermatogenic arrest, and male sterility. Surprisingly, LINE1 transposons are effectively silenced in MiwiRK mutant mice, indicating a LINE1-independent cause of germ cell arrest distinctive from Miwi knockout mice. These findings reveal a crucial function of the RG motif in directing PIWI proteins to engage in efficient piRNA production critical for germ cell progression and highlight the functional importance of the PIWI N-terminal motifs in regulating male fertility.
MeSH term(s)	Male ; Mice ; Animals ; Piwi-Interacting RNA ; Testis/metabolism ; RNA, Small Interfering/metabolism ; Spermatogenesis/genetics ; Proteins/metabolism ; Mice, Knockout ; Arginine/metabolism ; Argonaute Proteins/genetics ; Argonaute Proteins/metabolism ; Mammals/genetics
Chemical Substances	Piwi-Interacting RNA ; RNA, Small Interfering ; Proteins ; Arginine (94ZLA3W45F) ; Argonaute Proteins
Language	English
Publishing date	2023-11-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	2186725-2
ISSN	1553-7404 ; 1553-7390
ISSN (online)	1553-7404
ISSN	1553-7390
DOI	10.1371/journal.pgen.1011031
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Article ; Online: Effects of Notch2 on proliferation, apoptosis and steroidogenesis in bovine luteinized granulosa cells.

Li, Yating / Jing, Jiongjie / Dang, Wenqing / Han, Qi / Guo, Xiangyu / Jia, Kaiqi / Cheng, Ying / Wang, Kai / Kebreab, Ermias / Lyu, Lihua

Theriogenology

2021 Volume 171, Page(s) 55–63

Abstract: Notch signaling pathway plays an important regulatory role in the development of mammalian follicles. This study aimed to explore the effect of Notch2 on the function of bovine follicles luteinized granulosa cells (LGCs). We detected that the coding ... ...

Abstract	Notch signaling pathway plays an important regulatory role in the development of mammalian follicles. This study aimed to explore the effect of Notch2 on the function of bovine follicles luteinized granulosa cells (LGCs). We detected that the coding sequence (CDS) of bovine Notch2 gene is 7416 bp, encoding 2471 amino acids (AA). The homology of Notch2 AA sequence between bovine and other species is 86.04%-98.75%, indicating high conservatism. Immunohistochemistry found that Notch2 receptor and its ligand Jagged2 localize in granulosa cells (GCs) and theca cells in bovine antral follicles. And immunofluorescence found that positive signals of Notch2 and Jagged2 overlap in bovine LGCs, speculating that Notch2 receptor may react with Jagged2 ligand to activate Notch signaling pathway and play an important role in bovine LGCs. To further investigate the function of Notch2, Notch2 gene was silenced by short hairpin RNA (shRNA) and CCK-8 analysis showed that the proliferation rate of LGCs was downregulated significantly (P < 0.01). Quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that the mRNA expression of apoptosis related gene Bcl-2/Bax decreased (P < 0.01) and Caspase3 increased (P < 0.05), cell cycle related gene CyclinD2/CDK4 complex decreased (P < 0.01) and P21 increased (P < 0.05), steroidogenesis gene STAR and 3β-HSD decreased (P < 0.01) while CYP19A1 and CYP11A1 had no significant difference (P > 0.05). In addition, Enzyme-linked immunosorbent assay (ELISA) showed that there was no difference in estradiol (E
MeSH term(s)	Animals ; Apoptosis ; Cattle ; Cell Proliferation ; Estradiol ; Female ; Granulosa Cells ; Progesterone ; Receptor, Notch2/genetics ; Theca Cells
Chemical Substances	Receptor, Notch2 ; Progesterone (4G7DS2Q64Y) ; Estradiol (4TI98Z838E)
Language	English
Publishing date	2021-05-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	189232-0
ISSN	1879-3231 ; 0093-691X
ISSN (online)	1879-3231
ISSN	0093-691X
DOI	10.1016/j.theriogenology.2021.05.009
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