Zheng S.-J.,Chongqing Medical University |
Zheng S.-J.,Key Laboratory of High Altitude Medicine |
Zheng S.-J.,Key Laboratory of High Altitude Physiology and High Altitude Disease |
Tian H.-J.,Chongqing Medical University |
And 6 more authors.
Toxicology and Applied Pharmacology | Year: 2010
Di(n-butyl)phthalate (DBP) and benzo(a)pyrene (BaP) are environmental endocrine disruptors that are potentially hazardous to humans. These chemicals affect testicular macrophage immuno-endocrine function and testosterone production. However, the underlying mechanisms for these effects are not fully understood. It is well known that interleukin-1 beta (IL-1β), which is secreted by testicular macrophages, plays a trigger role in regulating Leydig cell steroidogenesis. The purpose of this study was to reveal the effects of co-exposure to DBP and BaP on testicular macrophage subset expression, IL-1β secretion and testosterone production. Adult male Sprague-Dawley rats were randomly divided into seven groups; two groups received DBP plus BaP (DBP+BaP: 50+1 or 250+5mg/kg/day) four groups received DBP or BaP alone (DBP: 50 or 250mg/kg/day; BaP: 1 or 5mg/kg/day), and one group received vehicle alone (control). After co-exposure for 90days, the relative expression of macrophage subsets and their functions changed. ED2+ testicular macrophages (reactive with a differentiation-related antigen present on the resident macrophages) were activated and IL-1β secretion was enhanced. DBP and BaP acted additively, as demonstrated by greater IL-1β secretion relative to each compound alone. These observations suggest that exposure to DBP plus BaP exerted greater suppression on testosterone production compared with each compound alone. The altered balance in the subsets of testicular macrophages and the enhanced ability of resident testicular macrophages to secrete IL-1β, resulted in enhanced production of IL-1β as a potent steroidogenesis repressor. This may represent an important mechanism by which DBP and BaP repress steroidogenesis. © 2010 Elsevier Inc. Source
Luo H.,Chongqing Medical University |
Luo H.,Key Laboratory of High Altitude Medicine |
Huang J.,Chongqing Medical University |
Huang J.,Key Laboratory of High Altitude Medicine |
And 7 more authors.
British Journal of Nutrition | Year: 2011
Hypoxia frequently occurs under several different cellular circumstances. Excess reactive oxygen species that are induced by hypoxia may result in cell injury and dysfunction. Recently, garlic has been found to possess some biological and pharmacological activities. The present study examined the effects of garlic saponins (GSP) on the survival of differentiated PC12 (dPC12) cells and the oxidative-antioxidant system. dPC12 cells were exposed to 2% O2 in order to establish a neuronal insult model. Cell viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide reduction assay and lactate dehydrogenase (LDH) release assay. The expression of selected genes (catalase (CAT), p65 and neuron-specific class III α-tubulin) was evaluated by real-time PCR and immunoblot assays. CAT activity, malondialdehyde (MDA) and 8-hydroxy-deoxyguanosine (8-OH-dG) concentrations were also determined. The data showed that hypoxia dramatically damaged dPC12 cells, while treatment with approximately 5×10 2-10ng/ml GSP improved cell viability, decreased LDH leakage and caused the cells to maintain neuronal-like characteristics in hypoxia. The production of MDA and 8-OH-dG was attenuated by GSP. CAT activity in dPC12 cells pretreated with GSP was higher than that of the hypoxic control. Moreover, GSP up-regulated CAT expression and decreased the total protein expression as well as the nuclear expression of p65 in hypoxic cells. These data indicate that GSP has antioxidant properties that can protect dPC12 cells from hypoxia-induced damage, which may be related to the up-regulation of CAT expression and activity as well as a decrease in the expression and nucleus distribution of p65 through effects on redox-sensitive signalling pathways. © 2010 The Authors. Source
Li P.,Chongqing Medical University |
Li P.,Key Laboratory of High Altitude Medicine |
Li P.,Key Laboratory of High Altitude Physiology and High Altitude Disease |
Huang J.,Chongqing Medical University |
And 14 more authors.
Experimental Hematology | Year: 2011
Objective: Hypoxia at high altitudes can lead to increased production of red blood cells through the hormone erythropoietin (EPO). In this study, we observed how the EPO-unresponsive hematopoietic stem cell (HSC) compartment responds to high-altitude hypoxic environments and contributes to erythropoiesis. Materials and Methods: Using a mouse model at simulated high altitude, the bone marrow (BM) and spleen lineage marker-Sca-1+c-Kit+ (LSK) HSC compartment were observed in detail. Normal LSK cells were then cultured under different conditions (varying EPO levels, oxygen concentrations, and BM supernatants) to investigate the causes of the HSC responses. Results: Hypoxic mice exhibited a marked expansion in BM and spleen LSK compartments, which were associated with enhanced proliferation. BM HSCs seemed to play a more important role in erythropoiesis at high altitude than spleen HSCs. There was also a lineage fate change of BM HSCs in hypoxic mice that was manifested in increased megakaryocyte-erythrocyte progenitors and periodically reduced granulocyte-macrophage progenitors in the BM. The LSK cells in hypoxic mice displayed upregulated erythroid-specific GATA-1 and downregulated granulocyte-macrophage-specific PU.1 messenger RNA expression, as well as the capacity to differentiate into more erythroid precursors after culture. BM culture supernatant from hypoxic mice (but not elevated EPO or varying O2 tension) could induce expansion and erythroid-priority differentiation of the HSC population, a phenomenon partially caused by increasing interleukin-3 and interleukin-6 secretion in the BM. Conclusions: The present study suggests a new EPO-independent HSC mechanism of high-altitude erythrocytosis. © 2011 ISEH - Society for Hematology and Stem Cells. Source