المؤلفون: Jingjing Cai, Yongping Huang, Hongyu Nie, Junjie Zhou, Peng Zhang, Xu Cheng, Yan Che, Yan-Xiao Ji, Zhi-Gang She, Zan Huang, Xiao-Jing Zhang, Haibo Xu, Jiaqi Sun, Dan Liu, Mao-Mao Gao, Guo-Peng Chen, Hongliang Li, Rufang Liao

المصدر: Cell metabolism. 31(4)

مصطلحات موضوعية: 0301 basic medicine, Drug, Nonalcoholic steatohepatitis, Physiology, Transgene, media_common.quotation_subject, Ubiquitin-Protein Ligases, Nerve Tissue Proteins, digestive system, TNFAIP3, Cell Line, 03 medical and health sciences, Mice, 0302 clinical medicine, Ubiquitin, Non-alcoholic Fatty Liver Disease, Animals, Humans, Metabolic Stress, Molecular Biology, Inhibitory effect, Tumor Necrosis Factor alpha-Induced Protein 3, media_common, biology, Chemistry, Intracellular Signaling Peptides and Proteins, nutritional and metabolic diseases, Cell Biology, MAP Kinase Kinase Kinases, digestive system diseases, Ubiquitin ligase, 030104 developmental biology, Liver, biology.protein, Cancer research, Carrier Proteins, 030217 neurology & neurosurgery

الوصف: Nonalcoholic steatohepatitis (NASH) is an unmet clinical challenge due to the rapid increase in its occurrence but the lack of approved drugs to treat it. Further unraveling of the molecular mechanisms underlying NASH may identify potential successful drug targets for this condition. Here, we identified TNFAIP3 interacting protein 3 (TNIP3) as a novel inhibitor of NASH. Hepatocyte-specific TNIP3 transgenic overexpression attenuates NASH in two dietary models in mice. Mechanistically, this inhibitory effect of TNIP3 is independent of its conventional role as an inhibitor of TNFAIP3. Rather, TNIP3 directly interacts with TAK1 and inhibits its ubiquitination and activation by the E3 ligase TRIM8 in hepatocytes in response to metabolic stress. Notably, adenovirus-mediated TNIP3 expression in the liver substantially blocks NASH progression in mice. These results suggest that TNIP3 may be a promising therapeutic target for NASH management.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8949e5602ec5cc0b32105571a09a200cTest
https://pubmed.ncbi.nlm.nih.gov/32268115Test

المؤلفون: Hiromitsu Nakajima, Hiroyuki Nakagawa, Hidemi Hatabayashi, Kimiko Yabe, Jingjing Cai, Hongmei Zeng

المصدر: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 21, Iss 6389, p 6389 (2020)
Volume 21
Issue 17

مصطلحات موضوعية: 0301 basic medicine, Aflatoxin, hypA (aflY), verA (aflN), 030106 microbiology, dmtA (aflO), ordB (aflX), Article, Catalysis, lcsh:Chemistry, Inorganic Chemistry, 03 medical and health sciences, chemistry.chemical_compound, enzyme gene, Biosynthesis, Gene cluster, Xanthone, ver-1 (aflM), Physical and Theoretical Chemistry, Binding site, lcsh:QH301-705.5, Molecular Biology, Spectroscopy, chemistry.chemical_classification, Enzyme Gene, Molecular mass, Organic Chemistry, General Medicine, Computer Science Applications, stcP, 030104 developmental biology, Enzyme, lcsh:Biology (General), lcsh:QD1-999, HAMA intermediate, chemistry, Biochemistry, aflatoxin biosynthesis

الوصف: In the biosynthesis of aflatoxin, verA, ver-1, ordB, and hypA genes of the aflatoxin gene cluster are involved in the pathway from versicolorin A (VA) to demethylsterigmatocystin (DMST). We herein isolated each disruptant of these four genes to determine their functions in more detail. Disruptants of ver-1, ordB, and hypA genes commonly accumulated VA in their mycelia. In contrast, the verA gene disruptant accumulated a novel yellow fluorescent substance (which we named HAMA) in the mycelia as well as culture medium. Feeding HAMA to the other disruptants commonly caused the production of aflatoxins B1 (AFB1) and G1 (AFG1). These results indicate that HAMA pigment is a novel aflatoxin precursor which is involved at a certain step after those of ver-1, ordB, and hypA genes between VA and DMST. HAMA was found to be an unstable substance to easily convert to DMST and sterigmatin. A liquid chromatography-mass spectrometry (LC-MS) analysis showed that the molecular mass of HAMA was 374, and HAMA gave two close major peaks in the LC chromatogram in some LC conditions. We suggest that these peaks correspond to the two conformers of HAMA
one of them would be selectively bound on the substrate binding site of VerA enzyme and then converted to DMST. VerA enzyme may work as a key enzyme in the creation of the xanthone structure of DMST from HAMA.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::55f3ed257706f6cb9ec7a034ef260debTest
https://doi.org/10.3390/ijms21176389Test

المؤلفون: Buhong Li, Jingjing Cai, Qiuping Zheng, Hui-Fang Huang

المصدر: Photodiagnosis and photodynamic therapy. 21

مصطلحات موضوعية: 0301 basic medicine, Cell Survival, Biophysics, Down-Regulation, Apoptosis, Dermatology, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Humans, Pharmacology (medical), Melanoma, bcl-2-Associated X Protein, TUNEL assay, Photosensitizing Agents, biology, Chemistry, Cytochrome c, Cytochromes c, Aminolevulinic Acid, Subcellular localization, Molecular biology, Mitochondria, Up-Regulation, Cytosol, 030104 developmental biology, Oncology, Terminal deoxynucleotidyl transferase, Photochemotherapy, Proto-Oncogene Proteins c-bcl-2, Cell culture, 030220 oncology & carcinogenesis, Caspases, biology.protein, Poly(ADP-ribose) Polymerases, A431 cells

الوصف: Objectives The purpose of this study was to investigate the effects of 5-aminolaevulinic acid mediated photodynamic therapy (ALA-PDT) on the survival activity and apoptosis of human melanoma cell line A375 and non-melanoma skin carcinoma cell line A431 cells. The mechanism for cellular apoptosis was explored. Methods The cell survival activity was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and the proportion of apoptotic cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression levels of Bcl-2, Bax, caspase-3, caspase-8 and caspase-9 protein were assessed by western blot. The subcellular localization of cytochrome c was comparatively investigated by immunohistochemistry between pre-ALA-PDT and post- ALA-PDT. Results ALA-PDT significantly inhibited the survival activity of A375 cells and A431 cells in a dose- and time-dependent manner. The optimum inhibition efficiencies for A375 cells and A431 cells were obtained at 0.6 mM ALA at 4 h and 8 h after ALA-PDT, respectively. The phenomena of apoptosis were observed in ALA-PDT treated cells by TUNEL assay. The apoptotic rates of A375 cells and A431 cells were 90.0% and 61.5% at 6 h after ALA-PDT, respectively. Apoptosis induced by ALA-PDT involved in down-regulation of Bcl-2 protein, up-regulation of Bax protein and cleaved-PARP protein. It was observed that the expression of cleaved- caspase-3, caspase-8 and caspase-9 proteins in A375 cells and A431 cells gradually increased in 2 h and 4 h but decreased at 4–6 h and 6–8 h after ALA-PDT, respectively. In apoptosis cells immunohistochemical localization show that cytochrome C diffused from the mitochondria into the cytosol. Conclusion ALA-PDT could significantly inhibit the survival activity of A375 and A431 cells. The apoptosis induced by ALA-PDT in A375 and A431 cells was related to the caspase-dependent death-receptor pathway and Cytochrome c-dependent mitochondrial pathway.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9ee04d6ca2422495f309b575c9d4fa75Test
https://pubmed.ncbi.nlm.nih.gov/29309850Test