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Kinase Signals (kinase + signal)
Selected AbstractsEPIGALLOCATECHIN-3-GALLATE ATTENUATES CARDIAC HYPERTROPHY IN HYPERTENSIVE RATS IN PART BY MODULATION OF MITOGEN-ACTIVATED PROTEIN KINASE SIGNALSCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 9 2009Dan-Dan Chen SUMMARY 1It has been demonstrated that epigallocatechin-3-gallate (EGCG) inhibits cardiac hypertrophy through its antihypertensive and anti-oxidant effects. However, the underlying molecular mechanism is not clear. 2In the present study, we tested the hypothesis that EGCG attenuates transaortic abdominal aortic constriction (TAC)-induced ventricular hypertrophy by regulating mitogen-activated protein kinase (MAPK) signal pathways in hypertensive rats. Four groups of rats were used: (i) a sham-operated control group; (ii) an EGCG-treated (50 mg/kg per day, i.p., for 21 days) sham-operated group; (iii) a TAC group; and (iv) an EGCG-treated TAC group. Histological analysis of whole hearts and biochemical analyses of left ventricular (LV) tissue were used to investigate the effects of EGCG. 3The results showed that the LV myocyte diameter and the expression of atrial natriuretic peptide, brain natriuretic peptide and ,-myocardial heavy chain were significantly decreased in the EGCG-treated (50 mg/kg per day, i.p.) TAC group. Levels of reactive oxygen species and malondialdehyde in the lV were significantly reduced by EGCG in the TAC group. Total superoxide dismutase, catalase and glutathione peroxidase activities were decreased in the TAC group, and this decrease was significantly restored by EGCG treatment. Phosphorylation of extracellular signal-regulated kinase 2, p38 and c-Jun N-terminal kinase 1 was significantly reversed in the LV of EGCG-treated TAC rats (40%, 53% and 52%vs TAC, respectively), accompanied by significant inhibition of nuclear factor-,B and activator protein-1. Transaortic abdominal aortic constriction significantly upregulated LV expression of matrix metalloproteinase-9 from 32 ± 6 to 100 ± 12% and this increase was inhibited by EGCG treatment (from 100 ± 12 to 50 ± 15%). In addition, TAC decreased mitochondrial DNA copy number and the activity of respiratory chain complexes I (from 100 ± 7 to 68 ± 5%), III (from 100 ± 4 to 2 ± 5%) and IV (from 766 ± 2 to 100 ± 5%); this decrease was reversed by EGCG treatment to levels seen in sham-operated rats. 4In conclusion, EGCG attenuates TAC-induced ventricular hypertrophy in hypertensive rats in part by suppression of anti-oxidant enzymes and regulation of MAPK signals. [source] Opposing effects on TSC-22 expression by BMP and receptor tyrosine kinase signals in the developing feather tractDEVELOPMENTAL DYNAMICS, Issue 1 2002Cord E. Dohrmann Abstract TSC-22 (transforming growth factor-,,stimulated clone 22) belongs to a family of leucine zipper transcription factors that includes sequences from invertebrates and vertebrates. The single Drosophila family member, encoded by the bunched gene, serves to integrate opposing bone morphogenic protein (BMP) and epidermal growth factor (EGF) signals during oogenesis. Similarly, mammalian TSC-22 expression is regulated by several families of secreted signaling molecules in cultured cells. Here, we show that chick TSC-22 is dynamically expressed in the condensing feather bud, as well as in many tissues of the chick embryo. BMP-2/4, previously shown to inhibit bud development, repress TSC-22 expression during feather bud formation in vivo. Noggin, a BMP antagonist, promotes TSC-22 expression. EGF, TGF-,, and fibroblast growth factor all promote both feather bud development and TSC-22 expression; each can promote ectopic feather buds that are regularly spaced between existing feather buds. Thus, TSC-22 is a candidate to integrate small imbalances in receptor tyrosine kinase and BMP signaling during feather tract development to generate stable and reproducible morphogenetic responses. © 2001 Wiley-Liss, Inc. [source] Mitogen-activated protein kinases mediate interleukin-1,-induced receptor activator of nuclear factor-,B ligand expression in human periodontal ligament cellsJOURNAL OF PERIODONTAL RESEARCH, Issue 4 2007A. Oikawa Background and Objective:, Interleukin-1,-stimulated receptor activator of nuclear factor-,B ligand (RANKL) expression in human periodontal ligament cells is partially mediated by endogenous prostaglandin E2, whereas mitogen-activated protein kinases (MAPKs) are implicated in regulating various interleukin-1-responsive genes. We investigated herein the involvement of MAPKs in interleukin-1,-stimulated RANKL expression in human periodontal ligament cells. Material and Methods:, Human periodontal ligament cells were pretreated separately with specific inhibitors of MAPKs, including extracellular signal-regulated kinase, p38 MAPK and c-Jun N-terminal kinase, and subsequently treated with interleukin-1,. Following each treatment, the phosphorylation of each MAPK, the expression of RANKL, and the production of prostaglandin E2 were determined. RANKL activity was evaluated using an assay to determine the survival of prefusion osteoclasts. Results:, Interleukin-1, induced RANKL expression at the mRNA and protein levels, as well as RANKL activity in human periodontal ligament cells. Interleukin-1, also activated extracellular signal-regulated kinase, p38 MAPK, and c-Jun N-terminal kinase. Pretreatment with each MAPK inhibitor partially, but significantly, suppressed interleukin-1,-induced RANKL expression and its activity, as well as prostaglandin E2 production. Conclusion:, In human periodontal ligament cells, three types of MAPK inhibitor may abrogate RANKL expression and activity induced by interleukin-1,, directly or indirectly through partial suppression of prostaglandin E2 synthesis. In addition, extracellular signal-regulated kinase, p38 MAPK, and c-Jun N-terminal kinase signals may co-operatively mediate interleukin-1,-stimulated RANKL expression and its activity in those cells. [source] ,-catenin mediates insulin-like growth factor-I actions to promote cyclin D1 mRNA expression, cell proliferation and survival in oligodendroglial culturesGLIA, Issue 9 2010Ping Ye Abstract By promoting cell proliferation, survival and maturation insulin-like growth factor (IGF)-I is essential to the normal growth and development of the central nervous system. It is clear that IGF-I actions are primarily mediated by the type I IGF receptor (IGF1R), and that phosphoinositide 3 (PI3)-Akt kinases and MAP kinases signal many of IGF-I-IGF1R actions in neural cells, including oligodendrocyte lineage cells. The precise downstream targets of these signaling pathways, however, remain to be defined. We studied oligodendroglial cells to determine whether ,-catenin, a molecule that is a downstream target of glycogen synthase kinase-3, (GSK3,) and plays a key role in the Wnt canonical signaling pathway, mediates IGF-I actions. We found that IGF-I increases ,-catenin protein abundance within an hour after IGF-I-induced phosphorylation of Akt and GSK3,. Inhibiting the PI3-Akt pathway suppressed IGF-I-induced increases in ,-catenin and cyclin D1 mRNA, while suppression of GSK3, activity simulated IGF-I actions. Knocking-down ,-catenin mRNA by RNA interference suppressed IGF-I-stimulated increases in the abundance of cyclin D1 mRNA, cell proliferation, and cell survival. Our data suggest that ,-catenin is an important downstream molecule in the PI3-Akt-GSK3, pathway, and as such it mediates IGF-I upregulation of cyclin D1 mRNA and promotion of cell proliferation and survival in oligodendroglial cells. © 2010 Wiley-Liss, Inc. [source] | |||||||||||||