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Mathias Cobbaut, Rita Derua, Peter J Parker, Etienne Waelkens, Veerle Janssens, Johan Van Lint
The protein kinase D (PKD) family is regulated through multi-site phosphorylation, including autophosphorylation. For example, PKD displays in vivo autophosphorylation on Ser-742 (and Ser-738 in vitro) in the activation loop and Ser-910 in the C-tail (hPKD1 numbering). In this paper, we describe the surprising observation that PKD also displays in vitro autocatalytic activity towards a Tyr residue in the P+1 loop of the activation segment. We define the molecular determinants for this unusual activity and identify a Cys residue (C705 in PKD1) in the catalytic loop as of utmost importance...
June 22, 2018: FEBS Letters
Ji Young Oh, Han Na Suh, Gee Euhn Choi, Hyun Jik Lee, Young Hyun Jung, So Hee Ko, Jun Sung Kim, Chang Woo Chae, Chang-Kyu Lee, Ho Jae Han
BACKGROUND AND PURPOSE: Sonic hedgehog pathway (Shh) plays a central role in maintaining stem cell function and behavior in various processes related to self-renewal and tissue regeneration. However, the therapeutic effect of Shh on mouse embryonic stem cells (mESCs) has not yet been clearly described. Thus, we investigated the effect of Shh on the regulation of mESC behaviors as well as the effect of Shh-pretreated mESCs in skin wound healing. EXPERIMENTAL APPROACH: The present study investigated the underlying mechanisms of Shh signaling pathway in growth and motility of mESCs using western blot analysis, cell proliferation assay, and cell migration assay...
June 22, 2018: British Journal of Pharmacology
Yunhuan Liu, Qing Liu, John Hesketh, Da Huang, Fang Gan, Shu Hao, Shan Tang, Yanxia Guo, Kehe Huang
Hepatic fibrosis is a common pathological basis of liver cirrhosis and hepatocellular carcinomas. So, prevention and treatment of liver fibrosis is one of the crucial therapeutic goals in hepatology. Organic selenium, glutathione or probiotics supplementation could ameliorate hepatic fibrosis, respectively. The purpose of this study is to develop a novel selenium-glutathione-enriched probiotics (SGP) and to investigate its protective effect on CCl4 -induced liver fibrosis in rats. Yeast strains with the high-yield glutathione were isolated and identified by analysis of 26S ribosomal DNA sequences...
May 1, 2018: Journal of Nutritional Biochemistry
Shuangjiao Deng, Hongfei Wang, Heng Fan, Lijuan Zhang, Jianli Hu, Qing Tang, Zhexing Shou, Xingxing Liu, Dongmei Zuo, Jia Yang, Meng Xu, Qianyun Chen, Yalan Dong, Zhen Nan, Hui Wu, Yujin Liu
Our study was to explore the potential role of miRNA-200b in modulating tumorigenesis in the model of ulcerative colitis-related colorectal cancer (UCRCC) and, further, to decipher the underlying mechanisms associated with this effect. In this study, we examined a greater number of polyps or adenomas, a higher grade of epithelial dysplasia accompanied with a decrease in survival ratio in azoxymethane (AOM)/dextran sulfate sodium (DSS) model mice compared to mice treated with over-expressed miRNA-200b. Surprisingly, enforced miRNA-200b expression significantly suppressed AOM/DSS-induced up-regulation of oncologic markers including β-catenin and CD133...
June 19, 2018: International Immunopharmacology
Murad Helaleh, Ilhame Diboun, Nada Al-Tamimi, Haya Al-Sulaiti, Mohamed Al-Emadi, Aishah Madani, Nayef A Mazloum, Aishah Latiff, Mohamed A Elrayess
BACKGROUND: Polybrominated diphenyl ethers (PBDEs), a widely utilized class of flame retardants in various commercial products, represent a prominent source of environmental contaminants. PBDEs tend to accumulate in adipose tissue, potentially altering the function of this endocrine organ and increasing risk of insulin resistance. The aim of this study was to compare levels of PBDEs in adipose tissues from two metabolically distinct obese groups; the insulin sensitive (IS) and the insulin resistant (IR)...
June 18, 2018: Chemosphere
In-Sung Song, Yu Jeong Jeong, Seung Hun Jeong, Hyoung Kyu Kim, Nam-Chul Ha, MyungGeun Shin, Kyung Soo Ko, Byoung Doo Rhee, Sungbo Shim, Sung-Wuk Jang, Jin Han
Multiple myeloma (MM) is a neoplastic plasma cell disorder with high disease recurrence rates. Novel therapeutic approaches capable of improving outcomes in patients with MM are urgently required. The AKT signalling plays a critical regulatory role in MM pathophysiology, including survival, proliferation, metabolism, and has emerged as a key therapeutic target. Here, we identified a novel AKT inhibitor, HS1793, and defined its mechanism of action and clinical significance in MM. HS1793 disrupted the interaction between AKT and heat shock protein 90, resulting in protein phosphatase 2A-modulated phosphorylated-AKT (p-AKT) reduction...
June 19, 2018: Cancer Letters
Wataru Komatsu, Hisashi Kishi, Kazumi Yagasaki, Shuji Ohhira
Urolithin A, a gut microbial metabolite of ellagic acid, is reported to exert anti-inflammatory effects in vitro and in vivo. However, complete mechanisms underlying the regulation of inflammatory responses by urolithin A remain unclear. This study aimed to evaluate the anti-inflammatory potential of urolithin A and its underlying mechanisms in lipopolysaccharide (LPS)-stimulated RAW264 macrophages. Urolithin A significantly attenuated the pro-inflammatory mediator production in LPS-stimulated RAW264 and mouse peritoneal macrophages...
June 19, 2018: European Journal of Pharmacology
Hong-Bin Wang, Tao Li, Dong-Zhou Ma, Hua Zhi
Neuroblastoma is the most common cancer in infants and the third most common cancer in children after leukemia and brain cancer. The purpose of our study was to investigate the effects of estrogen receptor (ER)-α36 gene silencing on tau protein phosphorylation, cell proliferation, and cell apoptosis in human neuroblastoma SH-SY5Y cells. SH-SY5Y cells were treated with estrogen or left untreated, to investigate the effects of estrogen stimulation on ERα36 and the ERK/protein B kinase (AKT) signaling pathway...
June 22, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Kelly A Hyndman, Chin-Rang Yang, Hyun Jun Jung, Ezigbobiara N Umejiego, Chung-Ling Chou, Mark A Knepper
Phosphorylation and lysine (K)-acetylation are dynamic post-translational modifications of proteins. Previous proteomic studies have identified over 170,000 phosphorylation sites, and 15,000 K-acetylation sites in mammals. We recently reported that the inner medullary collecting duct (IMCD), which functions in the regulation of water-reabsorption, via the actions of vasopressin, expresses many of the enzymes that can modulated K-acetylation. The purpose of this study was to determine the K-acetylated or phosphorylated proteins expressed in IMCD cells...
June 22, 2018: Physiological Genomics
Taylor Howard, Amara Greer-Short, Tony Satroplus, Nehal Patel, Drew Nassal, Peter J Mohler, Thomas J Hund
The mechanisms underlying CaMKII-induced arrhythmias in ischemia/reperfusion (I/R) are not fully understood. In this study, we tested the hypothesis that CaMKII increases late Na+ current (INa,L ) via phosphorylation of Nav 1.5 at Ser571 during I/R, thereby increasing arrhythmia susceptibility. To test our hypothesis, isolated, Langendorff-perfused hearts from wildtype (WT) mice and mice expressing Nav channel variants Nav 1.5-Ser571E (S571E) and Nav 1.5-Ser571A (S571A) were studied. Wildtype (WT) hearts showed a significant increase in the levels of phosphorylated CaMKII and Nav 1...
June 22, 2018: American Journal of Physiology. Heart and Circulatory Physiology
Masashi Mizuno, Atsushi Kuno, Toshiyuki Yano, Takayuki Miki, Hiroto Oshima, Tatsuya Sato, Kei Nakata, Yukishige Kimura, Masaya Tanno, Tetsuji Miura
To explore mechanisms by which SGLT2 inhibitors protect diabetic hearts from heart failure, we examined the effect of empagliflozin (Empa) on the ultrastructure of cardiomyocytes in the noninfarcted region of the diabetic heart after myocardial infarction (MI). OLETF, a rat model of type 2 diabetes, and its nondiabetic control, LETO, received a sham operation or left coronary artery ligation 12 h before tissue sampling. Tissues were sampled from the posterior ventricle (i.e., the remote noninfarcted region in rats with MI)...
June 2018: Physiological Reports
Brandee Decker, Kevin Pumiglia
Nitric oxide, produced by eNOS, plays critical roles in the regulation of vascular function and maintenance. Chronic PI3K signaling has recently been associated with vascular malformations. A well described substrate downstream of PI3K signaling is eNOS. Another critical downstream target of PI3K is the metabolic regulator, mTORc1. The relationship between mTORc1 and eNOS regulation, has not been determined. We generated cells with manipulated PI3K signaling by expressing the activating mutation, PIK3CAH1047R , or knocking down PTEN expression...
June 2018: Physiological Reports
Julie C Nielsen, Cathrine Nordgaard, Maxim A X Tollenaere, Simon Bekker-Jensen
Centriolar satellites (CS) are small proteinaceous granules that cluster around the centrosome and serve as cargo vehicles for centrosomal proteins. It is generally accepted that CS support a number of canonical and specialized centrosome functions. Consequently, these highly dynamic structures are the target of regulation by several cellular signalling pathways. Two decades of research have led to the identification of a large number of molecular components and new biological roles of CS. Here, we summarize the latest advances in the continuous efforts to uncover the compositional, functional, dynamic and regulatory aspects of CS...
June 22, 2018: Cells
David R Stevens, Sharon Hammes-Schiffer
The enzyme human DNA polymerase η (Pol η) is critical for bypassing lesions during DNA replication. In addition to the two Mg2+ ions aligning the active site, experiments suggest that a third Mg2+ ion could play an essential catalytic role. Herein the role of this third metal ion is investigated with quantum mechanical/molecular mechanical (QM/MM) free energy simulations of the phosphoryl transfer reaction and a proposed self-activating proton transfer from the incoming nucleotide to the pyrophosphate leaving group...
June 22, 2018: Journal of the American Chemical Society
Pedro Paulo Gattai, Edgar Maquigussa, Antonio da Silva Novaes, Rosemara da Silva Ribeiro, Vanessa Araújo Varela, Milene Subtil Ormanji, Mirian Aparecida Boim
Acute kidney injury is mostly reversible, and hepatocyte growth factor (HGF) has a relevant role in the tissue repair. MicroRNA (miR)-26a is an endogenous modulator of HGF. The role of miR-26a in the kidney repair process was evaluated in Wistar rats submitted to an acute kidney injury model of rhabdomyolysis induced by glycerol (6 mL/kg). Animals were evaluated 3, 12, 48, 96, and 120 hours after glycerol injection. Serum creatinine (SCr) and gene expression of HGF, c-met, signal transducer and activator of transcription 3 (STAT3), and miR-26a were estimated...
June 22, 2018: Journal of Cellular Biochemistry
Yanni Yin, Zhihui Wang, Danni Cheng, Xiang Chen, Yun Chen, Zhonghua Ma
ATP-binding cassette (ABC) transporters act mainly to transport compounds across cellular membranes and are important for diverse biological processes. However, their roles in pathogenesis have not been well-characterized in Fusarium graminearum. Sixty F. graminearum ABC protein genes were functionally characterized. Among them, FgArb1 regulates normal growth and importantly is essential for pathogenicity. Thus, the regulatory mechanisms of FgArb1 in pathogenicity were analyzed in this study. FgArb1 interacts with the mitogen-activated protein kinase (MAPK) FgSte7, and partially modulates plant penetration by regulating the phosphorylation of FgGpmk1 (the downstream kinase of FgSte7)...
June 22, 2018: New Phytologist
Dinesh Thummuri, Lalita Guntuku, Veerabhadra Swamy Challa, Ravinder Naik Ramavat, Vegi Ganga Modi Naidu
Osteoporosis is a major debilitating cause of fractures and decreases the quality of life in elderly patients. Bone homeostasis is maintained by bone forming osteoblasts and bone resorpting osteoclasts. Substantial evidences have shown that targeting osteoclasts using natural products is a promising strategy for the treatment of osteoporosis. In the current study, we investigated the osteoprotective effect of Abietic acid (AA) in in vitro and in vivo models of osteolysis. In vitro experiments demonstrated that, AA suppressed receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis and F-actin ring formation in a concentration dependent manner...
June 22, 2018: Journal of Cellular Physiology
Veronique A J Smits, Elisa Cabrera, Raimundo Freire, David A Gillespie
Claspin was discovered as a Chk1-interacting protein necessary for Chk1 phosphorylation and activation by the upstream kinase, ATR, in response to DNA synthesis inhibition in Xenopus oocyte extracts. Subsequent investigations have defined a molecular model in which Claspin acts as an adaptor or scaffold protein to facilitate activation of Chk1 by ATR within a multi-protein complex that forms on single-stranded DNA at stalled replication forks and sites of DNA damage. Interestingly, Claspin is an unstable protein whose degradation via the proteasome is tightly regulated via ubiquitination and controlled by multiple ubiquitin ligases and de-ubiquitinases...
June 22, 2018: FEBS Journal
Run-Ze Li, Xing-Xing Fan, Dan-Feng Shi, Guo-Yuan Zhu, Yu-Wei Wang, Lian-Xiang Luo, Hu-Dan Pan, Xiao-Jun Yao, Elaine Lai-Han Leung, Liang Liu
OBJECTIVE: Lung cancer is the number one cancer in terms of both mortality and incidence. Cancer cells differ from normal cells in that they can reprogram their metabolism to support a rapid proliferation rate and alter oxidative phosphorylation processes toward lactic acid fermentation, even under aerobic conditions. Therefore we aimed to identify new compounds that might act as Pyruvate kinase M2 isoform (PKM2) activators and to investigate their anti-cancer efficacy in non-small cell lung cancer (NSCLC) cells...
June 21, 2018: Chemical Biology & Drug Design
Jun Xia, Weihui Zeng, Yumin Xia, Bingchuan Wang, Dehui Xu, Dingxin Liu, Michael G Kong, Yingying Dong
Cold atmospheric plasma (CAP) represents a promising therapy for selectively cancer killing. However, the mechanism of CAP-induced cancer cell death remains unclear. Here, we identified the tumor necrosis factor (TNF)-family members, especially Fas, and overloaded intracellular nitric oxide (NO) participated in CAP induced apoptosis in A375 and A875 melanoma cell lines, which was known as extrinsic apoptosis pathway. This progress was mediated by antagonistic protein of reactive oxygen species (ROS), Sestrin2...
June 22, 2018: Journal of Biophotonics
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