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Important Inhibitor (important + inhibitor)
Selected AbstractsCommonalities in the neurobiology between autism and fragile XJOURNAL OF INTELLECTUAL DISABILITY RESEARCH, Issue 10 2008R. Hagerman There is a close association between autism and fragile X syndrome (FXS) with 30% of males with FXS having autism and 2 to 7% of children with autism having the fragile X mutation. The protein that is missing or deficient in FXS, FMRP, is an RNA binding and transport protein which regulates the translation of many messages important for synaptic plasticity. Typically FMRP inhibits the translation of these messages, such that protein production increases when FMRP is absent. Some of these proteins are known to also cause autism when they are mutated including neuroligin 3 and 4 and the SHANK protein. Therefore, when FMRP is missing there is dysregulation of other proteins that are known to cause autism. FMRP is an important inhibitor of protein production in the metabotropic glutamate receptor 5 pathway (mGluR5) which leads to long term depression (LTD) or the weakening of synaptic connections. Therefore, when FMRP is missing there is enhanced mGluR5 activity leading to enhanced LTD and weak or immature synaptic connections. The use of mGluR5 antagonists to reverse the LTD in the animal models of FXS has led to reversal of the learning, behaviour and dendritic spine abnormalities in these animals. There are now initial studies taking place in humans regarding the use of mGluR5 antagonists to improve behaviour and cognition in FXS. It is likely that these mGluR5 antagonists will also be helpful in a subgroup of patients with non fragile X autism who have similar problems with hyperactivity, hyperarousal and anxiety to those seen in FXS. A second cause of autism is the fragile X premutation but this mechanism of involvement is related to RNA toxicity which perhaps stimulates neuroimmune problems and may mimic other causes of autism. Neurons with the premutation are more vulnerable to environmental toxicity and oxidative stress leading to early cell death. [source] The effect of genetic variants in the thrombin activatable fibrinolysis inhibitor (TAFI) gene on TAFI-antigen levels, clot lysis time and the risk of venous thrombosisBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2006C.H. Martini Summary Thrombin activatable fibrinolysis inhibitor (TAFI) is an important inhibitor of fibrinolysis. High TAFI antigen levels are associated with an increased risk of deep venous thrombosis (DVT). Because TAFI levels are partly determined genetically, we assessed the association between three TAFI gene polymorphisms (,438 G/A, 505 A/G and 1040 C/T), TAFI antigen levels and clot lysis times and the risk of DVT. Carriers of the 505G allele, which is associated with lower TAFI antigen levels than the 505A allele, showed an increased risk of DVT. This indicates that the relationship between TAFI and venous thrombosis is more complex than previously suggested. [source] The relationship between circulating osteoprotegerin levels and bone mineral metabolism in healthy womenCLINICAL ENDOCRINOLOGY, Issue 2 2004Ki Won Oh Summary objective, Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the RANK ligand. Moreover, OPG has been shown to be an important inhibitor of osteoclastogenesis in animal models. However, the relationship between circulating OPG levels and female bone status in human populations is unclear. In this study we undertook to investigate the relationship between circulating OPG levels and bone mineral metabolism in healthy women. patients and measurements, Our subjects were 287 women aged 37,73 years (mean age 51·5 years). The serum concentrations of OPG were determined by enzyme-linked immunosorbent assay (ELISA). The biochemical markers of bone turnover and FSH were measured using standard methods. Bone mineral densities at the lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. results, Postmenopausal women had a significantly higher mean value of serum OPG than premenopausal women (1358·5 ± 32·5 pg/ml vs. 1228·8 ± 33·3 pg/ml, P < 0·01). Serum OPG levels were positively correlated with age (r = 0·169, P < 0·01), as were urine deoxypyridinoline levels (r = 0·133, P < 0·05) and serum FSH levels (r = 0·187, P < 0·01) in a bivariate correlation analyses. In a multiple regression analysis, only urine calcium excretion was identified as a significant predictor for serum OPG levels. conclusions, Circulating OPG levels were found to be associated with urine calcium excretion and menopause in healthy women. Our observations suggest that circulating OPG levels reflect an antiresorptive activity in bone, and they are related to endogenous oestrogen levels. [source] Advanced oxidation protein products inhibit differentiation and activate inflammation in 3T3-L1 preadipocytes,JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2010Qiu Gen Zhou Accumulation of advanced oxidation protein products (AOPPs) is prevalent in metabolic syndromes, a condition with impaired preadipocytes differentiation. In the present study, we tested the hypothesis that AOPPs disturb preadipocyte differentiation. Exposure of 3T3-L1 preadipocytes to increased levels of AOPPs inhibited accumulation of intracellular triglyceride and decreased the expression of the essential markers of matured adipocytes, such as adipocyte fatty-acid-binding protein (aP2), CAAT/enhancer-binding protein (C/EBP)-,, and peroxisome proliferator-activated receptor (PPAR)-,, in response to standard adipogenic induction. Inhibitory effects of AOPPs on preadipocytes differentiation was time sensitive, which occurred at the early stage of differentiation. In the presence of AOPPs, induction of preadipocytes differentiation resulted in upregulated expression of C/EBP homologous protein (CHOP) and CUG-Triplet repeat-binding protein (CUGBP), two important inhibitors of preadipocytes differentiation. In addition, treatment with AOPPs increased abundance of C/EBP-,-liver enriched inhibitory protein (C/EBP-,-LIP), a truncated C/EBP-, isoform without adipogenic activity. Moreover, AOPPs-treated preadipocytes expressed a macrophage marker F4/80 and overexpressed tumor necrosis factor-, and interleukin-6 via nuclear factor-,B (NF-,B)-dependent pathway. However, blocking inflammation with NF-,B inhibitor failed to improve AOPPs-induced inhibition of preadipocytes differentiation. These data suggest that accumulation of AOPPs may inhibit differentiation of preadipocytes and activate inflammation in these cells. This information might have implication for understanding the impairment of preadipocytes differentiation and fat inflammation seen in metabolic syndrome. J. Cell. Physiol. 225: 42,51, 2010. © 2010 Wiley-Liss, Inc. [source] | ||||||||||