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SP600125 PD98059 SB203580

Thanasekaran Jayakumar, Kao-Chang Lin, Wan-Jung Lu, Chia-Ying Lin, Geraldine Pitchairaj, Jiun-Yi Li, Joen-Rong Sheu
Nobiletin, a bioactive polymethoxylated flavone, has been described to possess a diversity of biological effects through its antioxidant and anti-inflammatory properties. Vasodilator-stimulated phosphoprotein (VASP) is a common substrate for cyclic AMP and cyclic GMP-regulated protein kinases [i.e., cyclic AMP-dependent protein kinase (PKA; also known as protein kinase A) and cyclic GMP-dependent protein kinase (PKG; also known as protein kinase G)] and it has been shown to be directly phosphorylated by protein kinase C (PKC)...
January 2017: International Journal of Molecular Medicine
Chang-Bum Ahn, Jae-Young Je, Young-Sang Kim, Sun-Joo Park, Boo Il Kim
Chemical modification of chitosan is a promising method for the improvement of biological activity. In this study, chitosan-caffeic acid (CCA) was prepared and its in vitro hepatoprotective ability against hydrogen peroxide-induced hepatic damage in liver cells was evaluated. Treatment with CCA (50-400 µg/mL) did not show cytotoxicity and also significantly (p < 0.05) recovered cell viability against 650 µM hydrogen peroxide-induced hepatotoxicity. CCA treatment attenuated reactive oxygen species generation and lipid peroxidation in addition to increasing cellular glutathione level in cultured hepatocytes...
January 2017: Molecular and Cellular Biochemistry
Helmut Schweikl, Matthias Widbiller, Stephanie Krifka, Johannes Klement, Christine Petzel, Carola Bolay, Karl-Anton Hiller, Wolfgang Buchalla
OBJECTIVE: Lipopolysaccharide (LPS) from cariogenic microorganisms and resin monomers like HEMA (2-hydroxyethyl methacrylate) included in dentin adhesive are present in a clinical situation in deep dentinal cavity preparations. Here, cell survival, expression of proteins related to redox homeostasis, and viability of mouse macrophages exposed to LPS and HEMA were analyzed with respect to the influence of oxidative stress. METHODS: Cell survival of RAW264.7 mouse macrophages was determined using a crystal violet assay, protein expression was detected by Western blotting, and HEMA- or LPS-induced apoptosis (cell viability) was analyzed by flow cytometry...
December 2016: Dental Materials: Official Publication of the Academy of Dental Materials
Yen-Yu Lu, Yung-Kuo Lin, Yu-Hsun Kao, Cheng-Chih Chung, Yung-Hsin Yeh, Shih-Ann Chen, Yi-Jen Chen
The extracellular matrix (ECM) and transforming growth factor-β (TGF)-β are important in cardiac fibrosis, however, the effects of the ECM on TGF‑β signaling remain to be fully elucidated. The aims of the present study were to evaluate the role of collagen in TGF‑β signaling and examine the underlying mechanisms. In the present study, western blot analysis was used to examine TGF‑β signaling in HL‑1 cells treated with and without (control) type I collagen (10 µg/ml), which was co‑administered with either an anti‑β1 integrin antibody (10 µg/ml) or a stretch‑activated channel inhibitor (gadolinium; 50 µM)...
October 2016: Molecular Medicine Reports
Qi Li, Fuxiang Bao, Dafu Zhi, Moning Liu, Qin Yan, Xinxin Zheng, Lixin Ren, Shan Cong, Yan Li, Guifang Cao
BACKGROUND: Beta defensins are secreted from ovine oviduct epithelial cells (OOECs) in response to microbial infection, and are potential alternatives to antibiotic agents in the treatment of microorganism infection, particularly given the abuse of antibiotic agents and the increasing number of drug-resistant bacteria. The aberrant expression of defensins may result in disorders involving organ and oviduct inflammation, such as salpingitis. METHODS: In the present study, we investigated the effects of LPS on the mRNA expression levels of sheep β-defensin-1 (SBD-1) in ovine oviduct epithelial cells...
August 11, 2016: Lipids in Health and Disease
Takamitsu Sasaki, Keita Inami, Yoshihiro Numata, Kodai Funakoshi, Midori Yoshida, Takeshi Kumagai, Shuichi Kanno, Satomi Matsui, Takayoshi Toriyabe, Yasushi Yamazoe, Kouichi Yoshinari, Kiyoshi Nagata
Multidrug resistance-associated protein 3 (MRP3) is a basolaterally localized transporter in the liver and contributes to the transport of various metabolites such as conjugates of endogenous compounds and drugs from hepatocytes. MRP3 expression in the human liver is low under normal physiologic conditions but is induced by drug treatment. Although several studies have identified a region necessary for the basal transcription of MRP3, no region that responds to drugs has been reported. To identify the xenobiotic-responsive elements of MRP3, we constructed a luciferase reporter plasmid containing the MRP3 5'-flanking region up to -10 kb upstream from the transcription start site...
October 2016: Journal of Pharmacology and Experimental Therapeutics
Renjun Wang, Wen Zhang, Zengxiang Dong, Yunfeng Qi, Michael Hultström, Xiaofu Zhou, En Yin Lai
AIM: Prostaglandin E2 mediates sympathoexcitation in chronic heart failure (CHF) through EP3 receptors (PTGER3) in the paraventricular nucleus (PVN). The aim of the present study was investigate the role of c-Jun N-terminal kinase (JNK) in expressional regulation of gamma-aminobutyric acid signaling in PVN of CHF rats. METHODS: CHF was induced by left coronary ligation in wistar rats. Renal sympathetic nerve activity and mean arterial pressure responses to the PVN infusion were determined in anesthetized rats...
July 20, 2016: Acta Physiologica
Naohiro Yamamoto, Haruhiko Tokuda, Gen Kuroyanagi, Shingo Kainuma, Rie Matsushima-Nishiwaki, Kazuhiko Fujita, Osamu Kozawa, Takanobu Otsuka
Heat shock proteins (HSPs) are induced in response to various physiological and environmental conditions such as chemical and heat stress, and recognized to function as molecular chaperones. HSP22 (HSPB8), a low-molecular weight HSP, is ubiquitously expressed in many cell types. However, the precise role of HSP22 in bone metabolism remains to be clarified. In the present study, we investigated whether HSP22 is implicated in the transforming growth factor-β (TGF-β)-stimulated migration of osteoblast-like MC3T3-E1 cells...
November 15, 2016: Molecular and Cellular Endocrinology
Ji-Yun Park, Beom Su Kim, Jun Lee
Angiogenesis is an essential physiological step in wound healing and other regenerative processes. Here, we evaluated the angiogenic properties of an exopolysaccharide (EPS) secreted by MK1 (MK1-EPS), a novel bacterial strain isolated from Neungee mushrooms. MK1-EPS significantly increased human umbilical vein endothelial cell (HUVEC) proliferation, migration, and vascular tube formation. MK1-EPS enhanced the phosphorylation of extracellular signal-related kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, which are mitogen-activated protein kinases...
September 2016: Archives of Pharmacal Research
Sousuke Kanaya, Hidehiro Komatsu, Hidetoshi Shimauchi, Eiji Nemoto
PURPOSE/AIM: Glutamate is one of the signaling molecules responsible for transmission in the central nervous system. Periodontal ligament (PDL) cells were recently reported to express metabotropic glutamate receptors (mGluRs). However, the functions of mGluR signaling in PDL cells or PDL-related cells remain largely unknown. The aim of this study was to investigate the expression and function of mGluRs in PDL-related cells. MATERIALS AND METHODS: OCCM-30 cells, immortalized murine cementoblasts, were stimulated with l-glutamate or mGluRs antagonists...
September 2016: Connective Tissue Research
Chun Guo, Xu-Guang Yang, Fei Wang, Xu-Yuan Ma
Interleukin (IL)-1 is a proinflammatory cytokine that plays important roles in inflammation and host responses to infection. The present study aimed to evaluate the effects of IL-1α on the apoptosis and differentiation of osteoblasts, and to elucidate the mechanism responsible for these effects in the osteoblast‑like cell line MC3T3-E1. The MC3T3-E1 cells were non-treated or treated with IL-1α. Following treatment, cell viability, alkaline phosphatase (ALP) activity and caspase-3 activity were evaluated...
July 2016: International Journal of Molecular Medicine
Tingfang Yang, Shuluan Yao, Xianfeng Zhang, Yan Guo
T-cell acute lymphoblastic leukemia (T-ALL) as a prevalent hematologic malignancy is one of the most common malignant tumors worldwide in children. Andrographolide (Andro), the major active component from Andrographis paniculata, has been shown to possess antitumor activities in several types of cancer cells. However, whether Andro would inhibit T-ALL cell growth remains unclear. In this study, we investigated the cytotoxic effect of Andro on human T-ALL Jurkat cells and explored the mechanisms of cell death...
2016: Drug Design, Development and Therapy
Marwa Y Sallam, Sahar M El-Gowilly, Abdel-Galil A Abdel-Galil, Mahmoud M El-Mas
Reduced blood pressure (BP) and cardiac autonomic activity are early manifestations of endotoxemia. We investigated whether these effects are modulated by central mitogen-activated protein kinases (MAPKs) and related phosphoinositide-3-kinase (PI3K)/soluble guanylate cyclase (sGC) signaling in conscious rats. The effect of pharmacologic inhibition of these molecular substrates on BP, heart rate (HR), and heart rate variability (HRV) responses evoked by intravascular lipopolysaccharide (LPS) (10 mg/kg) were assessed...
August 2016: Journal of Cardiovascular Pharmacology
Shin-Saeng Lim, Sung-Ho Kook, Jeong-Chae Lee
Recombinant COMP-Ang1, a chimera of angiopoietin-1 (Ang1), and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP) can stimulate multiple cellular processes. Proliferative capacity of periodontal ligament (PDL) fibroblasts (PLFs) is important for maintaining PDL integrity and homeostasis. In this study, we explored whether exogenous COMP-Ang1 addition enhances proliferation of human PLFs and the cellular mechanisms therein. We initially isolated and characterized PLFs, where the cells showed highly positive staining for surface markers, CD90, CD105, and CD146...
May 2016: Molecular and Cellular Biochemistry
Ningning Dang, Shuguang Pang, Haiyan Song, Liguo An, Xiaoli Ma
OBJECTIVES: Several investigations have revealed that caspase-14 is responsible for the epidermal differentiation and cornification, as well as the regulation of moisturizing effect. However, the precise regulation mechanism is still not clear. This study was aimed to investigate the expression of caspase-14 in filaggrin-deficient normal human epidermal keratinocytes (NHEKs) and to explore the possible mechanism that contributes to the regulation of caspase-14. MATERIALS AND METHODS: The filaggrin-deficient NHEKs were induced by transfection with lentivirus (LV) vector encoding small hairpin RNAs (shRNA)...
January 2016: Iranian Journal of Basic Medical Sciences
Cheng Yin, Guang-Fu Huang, Xiao-Chuan Sun, Zongduo Guo, John H Zhang
BACKGROUND AND PURPOSE: Since tozasertib is neuroprotective for injured optic nerve, this study is intended to test whether tozasertib reduces early brain injury after subarachnoid hemorrhage (SAH) in a rat model. METHODS: Two hundred sixteen (216) male Sprague-Dawley rats were randomly subjected to endovascular perforation model of SAH and sham group. SAH grade, neurological score, and brain water content were measured at 24 and 72 h after SAH. Dual leucine zipper kinase (DLK) and its downstream factors, JNK-interacting protein 3 (JIP3), MA2K7, p-JNK/JNK (c-Jun N-terminal kinase), and apoptosis related proteins cleaved caspase-3 (CC-3), Bim, Bcl-2, and cleaved caspase-9 (CC-9) were analyzed by western blot at 24 h after SAH...
September 2016: Neuropharmacology
Liang Huang, Li-Feng Liu, Juan Liu, Ling Dou, Ge-Ying Wang, Xiao-Qing Liu, Qiong-Lan Yuan
Ginsenoside Rg1 (Rg1) has anti-aging and anti-neurodegenerative effects. However, the mechanisms underlying these actions remain unclear. The aim of the present study was to determine whether Rg1 affects hippocampal survival and neurite outgrowth in vitro after exposure to amyloid-beta peptide fragment 25-35 (Aβ25-35), and to explore whether the extracellular signal-regulated kinase (ERK) and Akt signaling pathways are involved in these biological processes. We cultured hippocampal neurons from newborn rats for 24 hours, then added Rg1 to the medium for another 24 hours, with or without pharmacological inhibitors of the mitogen-activated protein kinase (MAPK) family or Akt signaling pathways for a further 24 hours...
February 2016: Neural Regeneration Research
Qin Wang, Jianchun Wang, Mingdong Hu, Yu Yang, Liang Guo, Jing Xu, Chuanjiang Lei, Yan Jiao, JianCheng Xu
Uncoupling protein 2 (UCP2) is upregulated in patients with systemic inflammation and infection, but its functional role is unclear. We up- or downregulated UCP2 expression using UCP2 recombinant adenovirus or the UCP2 inhibitor, genipin, in lungs of mice, and investigated the mechanisms of UCP2 in ALI. UCP2 overexpression in mouse lungs increased LPS-induced pathological changes, lung permeability, lung inflammation, and lowered survival rates. Furthermore, ATP levels and mitochondrial membrane potential were decreased, while reactive oxygen species production was increased...
2016: Mediators of Inflammation
Silvia Petrini, Tommaso Neri, Stefania Lombardi, Cinzia Cordazzo, Cristina Balìa, Valentina Scalise, Pierluigi Paggiaro, Roberto Pedrinelli, Alessandro Celi
BACKGROUND: Obesity is linked to increased thrombotic risk. Circulating leptin concentration correlates with body mass index. Microparticles are small (.05-1 μm) vesicles shed by activated and apoptotic cells, involved in numerous pathophysiologically relevant phenomena including blood coagulation and thrombosis. We tested the hypothesis that leptin induces the shedding of procoagulant, tissue factor bearing microparticles by human peripheral blood mononuclear cells, and investigated the intracellular mechanisms leading to microparticle release upon incubation with leptin...
June 2016: Biochimica et Biophysica Acta
Yu-Ping Hsieh, Hsin-Ming Chen, Hung-Ying Lin, Hsiang Yang, Jenny Zwei-Chieng Chang
BACKGROUND/PURPOSE: Transforming growth factor (TGF)-β is a key regulator in the pathogenesis of oral submucous fibrosis (OSF). Early growth response (Egr)-1 is essential for fibrotic responses to TGF-β. Because TGF-β signaling is cell-type- and context-dependent, we investigated the signaling involved in TGF-β-induced Egr-1 in primary human buccal mucosal fibroblasts (BMFs). METHODS: TGF-β-induced Egr-1 and its signaling were assessed by western blotting in BMFs...
February 24, 2016: Journal of the Formosan Medical Association, Taiwan Yi Zhi
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