Chen T.,University of Maryland, Baltimore |
Tompkins L.M.,University of Maryland, Baltimore |
Li L.,University of Maryland, Baltimore |
Li H.,University of Maryland, Baltimore |
And 3 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2010
The constitutive androstane receptor (CAR) is constitutively activated in immortalized cell lines independent of xenobiotic stimuli. This feature of CAR has limited its use as a sensor for xenobiotic-induced expression of drug-metabolizing enzymes. Recent reports, however, reveal that a splicing variant of human CAR (hCAR3), which contains an insertion of five amino acids (APYLT), exhibits low basal but xenobiotic-inducible activities in cell-based reporter assays. Nonetheless, the underlying mechanisms of this functional shift are not well understood. We have now generated chimeric constructs containing various residues of the five amino acids of hCAR3 and examined their response to typical hCAR activators. Our results showed that the retention of alanine (hCAR1+A) alone is sufficient to confer the constitutively activated hCAR1 to the xenobiotic-sensitive hCAR3. It is noteworthy that hCAR1+A was significantly activated by a series of known hCAR activators, and displayed activation superior to that of hCAR3. Moreover, intracellular localization assays revealed that hCAR1+A exhibits nuclear accumulation upon 6-(4-chlorophenyl) imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl) oxime (CITCO) treatment in COS1 cells, which differs from the spontaneous nuclear distribution of hCAR1 and the nontranslocatable hCAR3. Mammalian two-hybrid and glutathione S-transferase pulldown assays further demonstrated that hCAR1+A interacts with the coactivator SRC-1 and GRIP-1 at low level before activation, while at significantly enhanced level in the presence of CITCO. Thus, the alanine residue in the insertion of hCAR3 seems in charge of the xenobiotic response of hCAR3 through direct and indirect mechanisms. Activation of hCAR1+A may represent a sensitive avenue for the identification of hCAR activators. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics.
Zhao L.,National Institute for Occupational Health and Poison Control
Wei sheng yan jiu = Journal of hygiene research | Year: 2010
Myelin protein zero (P0) is the major structural element of peripheral myelin that plays a very important role in maintaining the stability of myelin. Recently, many researches find that the structure, distribution and function of P0 have transcended people's early understanding. In this review, the basic features of structure, distribution and function of P0 and its current research advances in neurotoxicology are simply summarized.
Guo X.,National Institute for Occupational Health and Poison Control
Zhonghua lao dong wei sheng zhi ye bing za zhi = Zhonghua laodong weisheng zhiyebing zazhi = Chinese journal of industrial hygiene and occupational diseases | Year: 2012
To evaluate the therapeutic effects of epidermal growth factor (EGF) combined with plasma cryoprecipitate (CRYO) on the corneal injury induced by paraquat (PQ). According to the "Toxicological test methods of pesticides for registration" (GB 15670-1995), the conjunctival sacs of 18 health New Zealand rabbits were exposed to 100 μl 20% PQ, which were randomly divided into EGF, CRYO and EGF plus CRYO groups. The routine treatments (normal saline washing and antibiotic eyedrops) were administrated to the injured eyes of 3 groups, at the same time the left eyes of 3 groups were treated with EGF, CRYO and EGF plus CRYO, respectively. The injury of conjunctival, iris and corneal, fluorescent stranded and pathology changes of corneal were observed. The injury score was calculated and the recovery time of corneal injury was recorded. The recovery time of corneal injury in EGF and EGF plus CRYO groups were 19.50 ± 3.08 and 18.67 ± 2.73 days, respectively which were significantly lower than those (27.33 ± 2.58 and 26.83 ± 3.13 days) in corresponding routine treatment controls (P < 0.05). EGF and EGF plus CRYO could be used to treat the corneal injury induced by paraquat.
Yang H.,National Institute for Occupational Health and Poison Control |
Dong H.,National Institute for Occupational Health and Poison Control |
Dai Y.,National Institute for Occupational Health and Poison Control |
Zheng Y.,National Institute for Occupational Health and Poison Control
Respirology | Year: 2011
Background and objective: Polymorphisms in the IL13 gene have been reported to be associated with susceptibility to asthma. However, a number of studies have shown inconsistent results. A meta-analysis was performed to investigate whether polymorphisms in the IL13 gene were associated with the risk of asthma. Methods: Searches were performed of the Medline and Chinese National Knowledge Infrastructure (CNKI) databases, covering all papers published up to 31 August 2010. A recently proposed logistic regression-based method for meta-analysis of case-control genetic association studies was used to analyse pooled data. All statistical analyses were performed using stata version 10.0 software. Results: The IL13 C-1112T and G+2044A polymorphisms were investigated in 10 and 14 studies, respectively. The summary estimates suggested that both these polymorphisms were associated with susceptibility to asthma. Carriers of the IL13 -1112T allele had a 38.9% increased risk of asthma compared with homozygotes (-1112CC) (odds ratio (OR) 1.389, 95% confidence interval (CI): 1.103-1.749). Carriers of the IL13+2044A allele had a 40.0% increased risk of asthma compared with homozygotes (+2044GG) (OR 1.400, 95% CI: 1.137-1.724). In a subgroup analysis by ethnicity, the IL13 -1112T allele was associated with an increased risk of asthma among Caucasians (OR 1.629, 95% CI: 1.255-2.113) but not among Asians, and the IL13+2044A allele was associated with an increased risk of asthma among Asians (OR 1.436, 95% CI: 1.101-1.873) but not among Caucasians. Conclusions: This meta-analysis indicated that the IL13 C-1112T and G+2044A polymorphisms predispose to asthma. Further studies, including pooling of individual data to facilitate evaluation of gene-gene and gene-environment interactions between these IL13 gene polymorphisms and asthma susceptibility, are recommended. A meta-analysis showed that both the IL13 C-1112T and G+2044A polymorphisms were associated with an increased risk of asthma. The C-1112T polymorphism was associated with an increased risk of asthma in Caucasian but not Asian populations. The G+2044A polymorphism was associated with an increased risk of asthma in Asian but not Caucasian populations. © 2011 Asian Pacific Society of Respirology.
Yu T.,National Institute for Occupational Health and Poison Control
Wei sheng yan jiu = Journal of hygiene research | Year: 2010
To explore effects of lead exposure on the concentrations of serum male sex hormone in male workers. Blood sample of 153 male workers occupationally exposed to lead and 47 male worker without exposure history were collected, of which the concentrations of testosterone (T), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2) and inhibin B were measured by ELISA. The results showed that concentration of T in exposure group were significantly lower (P < 0.05) compared with non-exposured group. In contrast, serum inhibin B concentration were significantly increased (P < 0.05) than control group. The main influencing factors changing serum T are effect of lead and age, meanwhile positive effects of lead were also observed on serum inhibin B increased by Logistic analysis. The results suggest that the lead exposure may alter the male sexual hormone, which might injure the endocrine function and Sertoli cells.