6 results on '"Denghong Zhang"'
Search Results
2. High activity chimeric snake gamma-type phospholipase A
- Author
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Shimin, Sun, Denghong, Zhang, Jing, Zhang, Chunhong, Huang, and Ying, Xiong
- Subjects
Mice ,Liver ,Phospholipase A2 Inhibitors ,Colubridae ,Escherichia coli ,Animals ,Protein Isoforms ,Bacteriophages ,DNA Shuffling ,Hemorrhage ,Amino Acid Sequence ,Sequence Alignment ,Snake Venoms - Abstract
The gamma-type inhibitor of snake venom phospholipase A
- Published
- 2018
3. The inhibitory effect of saPLIγ, a snake sourced PLA
- Author
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Denghong, Zhang, Jingjing, Li, Shimin, Sun, and Chunhong, Huang
- Subjects
Inflammation ,Mice ,Phospholipases A2 ,Cyclooxygenase 2 ,Phospholipase A2 Inhibitors ,Tumor Necrosis Factor-alpha ,Interleukin-1beta ,Colubridae ,Animals ,Carrageenan ,Gene Expression Regulation, Enzymologic ,Snake Venoms - Abstract
SaPLIγ is a natural phospholipase A
- Published
- 2018
4. Exploration of the Inhibitory Potential of Varespladib for Snakebite Envenomation
- Author
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Jing Zhang, Huixiang Xiao, Denghong Zhang, Chunhong Huang, Yiding Wang, and Shengwei Xiong
- Subjects
0301 basic medicine ,Indoles ,Antivenom ,Ecchymosis ,Pharmaceutical Science ,Snake Bites ,Venom ,Pharmacology ,Acetates ,Analytical Chemistry ,chemistry.chemical_compound ,Mice ,Drug Discovery ,Medicine ,Edema ,Creatine Kinase ,biology ,Antivenins ,Alanine Transaminase ,Keto Acids ,Isoenzymes ,Chemistry (miscellaneous) ,Snake venom ,Molecular Medicine ,Female ,antivenom ,myotoxicity ,phospholipase A2 ,varespladib ,Phospholipase A2 Inhibitors ,Myotoxin ,Aspartate transaminase ,complex mixtures ,Article ,lcsh:QD241-441 ,03 medical and health sciences ,lcsh:Organic chemistry ,Crotalid Venoms ,Animals ,Aspartate Aminotransferases ,Physical and Theoretical Chemistry ,Envenomation ,Muscle, Skeletal ,L-Lactate Dehydrogenase ,business.industry ,Organic Chemistry ,Phospholipases A2 ,030104 developmental biology ,chemistry ,Alanine transaminase ,biology.protein ,Varespladib ,business ,Crotalinae - Abstract
Phospholipase A2s (PLA2) is a major component of snake venom with diverse pathologic toxicities and, therefore, a potential target for antivenom therapy. Varespladib was initially designed as an inhibitor of mammal PLA2s, and was recently repurposed to a broad-spectrum inhibitor of PLA2 in snake venom. To evaluate the protective abilities of varespladib to hemorrhage, myonecrosis, and systemic toxicities that are inflicted by different crude snake venoms, subcutaneous ecchymosis, muscle damage, and biochemical variation in serum enzymes derived from the envenomed mice were determined, respectively. Varespladib treatment showed a significant inhibitory effect to snake venom PLA2, which was estimated by IC50 in vitro and ED50 in vivo. In animal models, the severely hemorrhagic toxicity of D. acutus and A. halys venom was almost fully inhibited after administration of varespladib. Moreover, signs of edema in gastrocnemius muscle were remarkably attenuated by administration of varespladib, with a reduced loss of myonecrosis and desmin. Serum levels of creatine kinase, lactate dehydrogenase isoenzyme 1, aspartate transaminase, and alanine transaminase were down-regulated after treatment with varespladib, which indicated the protection to viscera injury. In conclusion, varespladib may be a potential first-line drug candidate in snakebite envenomation first aid or clinical therapy.
- Published
- 2018
5. MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice
- Author
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Denghong, Zhang, Riccardo, Contu, Michael V G, Latronico, Jianlin, Zhang, Jian Ling, Zhang, Roberto, Rizzi, Daniele, Catalucci, Shigeki, Miyamoto, Katherine, Huang, Marcello, Ceci, Yusu, Gu, Nancy D, Dalton, Kirk L, Peterson, Kun-Liang, Guan, Joan Heller, Brown, Ju, Chen, Nahum, Sonenberg, and Gianluigi, Condorelli
- Subjects
Cardiomyopathy, Dilated ,Male ,Cardiac function curve ,medicine.medical_specialty ,Cell Survival ,Apoptosis ,Cardiomegaly ,Cell Cycle Proteins ,mTORC1 ,Mechanistic Target of Rapamycin Complex 1 ,Mice ,Clinical investigation ,Internal medicine ,Eukaryotic initiation factor ,Animals ,Myocyte ,Medicine ,Initiation factor ,Myocytes, Cardiac ,Eukaryotic Initiation Factors ,Phosphorylation ,Mechanistic target of rapamycin ,PI3K/AKT/mTOR pathway ,Adaptor Proteins, Signal Transducing ,Mice, Knockout ,Pressure overload ,biology ,business.industry ,Cell growth ,Myocardium ,TOR Serine-Threonine Kinases ,Autophagy ,Proteins ,Heart ,General Medicine ,Phosphoproteins ,Cell biology ,Mice, Inbred C57BL ,Endocrinology ,Multiprotein Complexes ,Cardiology ,biology.protein ,Female ,Carrier Proteins ,Corrigendum ,business ,Transcription Factors ,Research Article - Abstract
Mechanistic target of rapamycin (MTOR) plays a critical role in the regulation of cell growth and in the response to energy state changes. Drugs inhibiting MTOR are increasingly used in antineoplastic therapies. Myocardial MTOR activity changes during hypertrophy and heart failure (HF). However, whether MTOR exerts a positive or a negative effect on myocardial function remains to be fully elucidated. Here, we show that ablation of Mtor in the adult mouse myocardium results in a fatal, dilated cardiomyopathy that is characterized by apoptosis, autophagy, altered mitochondrial structure, and accumulation of eukaryotic translation initiation factor 4E–binding protein 1 (4E-BP1). 4E-BP1 is an MTOR-containing multiprotein complex-1 (MTORC1) substrate that inhibits translation initiation. When subjected to pressure overload, Mtor-ablated mice demonstrated an impaired hypertrophic response and accelerated HF progression. When the gene encoding 4E-BP1 was ablated together with Mtor, marked improvements were observed in apoptosis, heart function, and survival. Our results demonstrate a role for the MTORC1 signaling network in the myocardial response to stress. In particular, they highlight the role of 4E-BP1 in regulating cardiomyocyte viability and in HF. Because the effects of reduced MTOR activity were mediated through increased 4E-BP1 inhibitory activity, blunting this mechanism may represent a novel therapeutic strategy for improving cardiac function in clinical HF.
- Published
- 2010
6. IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation
- Author
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Xiaoduo, Xie, Denghong, Zhang, Bin, Zhao, Min-Kan, Lu, Ming, You, Gianluigi, Condorelli, Cun-Yu, Wang, and Kun-Liang, Guan
- Subjects
Mice, Knockout ,Myocardium ,Amino Acid Motifs ,Mutation, Missense ,Fibroblasts ,Protein Serine-Threonine Kinases ,Biological Sciences ,I-kappa B Kinase ,Enzyme Activation ,Mice ,Cell Transformation, Neoplastic ,HEK293 Cells ,Rapamycin-Insensitive Companion of mTOR Protein ,Amino Acid Substitution ,Trans-Activators ,Animals ,Humans ,Naphthyridines ,Phosphorylation ,Carrier Proteins ,Proto-Oncogene Proteins c-akt ,HeLa Cells ,Transcription Factors - Abstract
AKT activation requires phosphorylation of the activation loop (T308) by 3-phosphoinositide-dependent protein kinase 1 (PDK1) and the hydrophobic motif (S473) by the mammalian target of rapamycin complex 2 (mTORC2). We recently observed that phosphorylation of the AKT hydrophobic motif was dramatically elevated, rather than decreased, in mTOR knockout heart tissues, indicating the existence of other kinase(s) contributing to AKT phosphorylation. Here we show that the atypical IκB kinase ε and TANK-binding kinase 1 (IKKε/TBK1) phosphorylate AKT on both the hydrophobic motif and the activation loop in a manner dependent on PI3K signaling. This dual phosphorylation results in a robust AKT activation in vitro. Consistently, we found that growth factors can induce AKT (S473) phosphorylation in Rictor(-/-) cells, and this effect is insensitive to mTOR inhibitor Torin1. In IKKε/TBK1 double-knockout cells, AKT activation by growth factors is compromised. We also observed that TBK1 expression is elevated in the mTOR knockout heart tissues, and that TBK1 is required for Ras-induced mouse embryonic fibroblast transformation. Our observations suggest a physiological function of IKKε/TBK1 in AKT regulation and a possible mechanism of IKKε/TBK1 in oncogenesis by activating AKT.
- Published
- 2011
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