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Title: Effects of sulfur dioxide on apoptosis-related gene expressions in lungs from rats

Abstract

Sulfur dioxide (SO{sub 2},) is an air pollutant in densely populated areas as well as in areas polluted by coal-fired power plants, smelters, and sulfuric acid factories. In the present study, male Wistar rats were housed in exposure chambers and treated with 14.00 {+-} 1.01, 28.00 {+-} 1.77, and 56.00 {+-} 3.44mg/m{sup 3} SO{sub 2} for 6h/day for 7 days, while control rats were exposed to filtered air in the same condition. The mRNA and protein levels of three apoptosis-related genes (p53 and bax are promoters of apoptosis, whereas bcl-2 is apoptotic suppressor) were analyzed in lungs using a real-time reverse transcription-polymerise chain reaction (real-time RT-PCR) assay and immunohistochemistry method, and caspase-3 activities were detected. The results showed that mRNA levels of p53 and bax were increased in a dose-dependent manner and at the concentrations of 28.00 and 56.00mg/m{sup 3} SO{sub 2} the increases were significant (for p53: 1.23-fold at 28 mg/m{sup 3} and 1.39-fold at 56 mg/m{sup 3}; for bax: 1.77-fold at 28 mg/m{sup 3} and 2.26-fold at 56 mg/m{sup 3}, respectively), while mRNA levels of bcl-2 were decreased significantly (0.78-fold at 28 mg/m{sup 3} and 0.73-fold at 56 mg/m{sup 3}) in lungs of rats exposed to SO{sub 2}.more » Dose-dependent increase of p53 and bax proteins in the lungs was observed after SO{sub 2} inhalation, while decrease of bcl-2 protein levels was obtained using immunohistochemistry method. Caspase-3 activities were increased in lungs of rats after SO{sub 2} inhalation. These results lead to a conclusion that SO{sub 2}, exposure can change the expression of apoptosis-related genes, and it suggests that SO{sub 2} can induce apoptosis in lung of rat and may have relations with some apoptosis-related diseases. Elucidating the expression patterns of those factors after SO{sub 2} inhalation may be critical to our understanding mechanisms of SO{sub 2} toxicity and helpful for the therapeutic intervention.« less

Authors:
;  [1]
  1. Shanxi University, Taiyuan (China)
Publication Date:
OSTI Identifier:
20700879
Resource Type:
Journal Article
Resource Relation:
Journal Name: Regulatory Toxicology and Pharmacology; Journal Volume: 43; Journal Issue: 3
Country of Publication:
United States
Language:
English
Subject:
01 COAL, LIGNITE, AND PEAT; SULFUR DIOXIDE; RATS; AIR POLLUTION; LUNGS; INHALATION; HEALTH HAZARDS; GENES; EXPOSURE CHAMBERS; PROTEINS

Citation Formats

Bai, J.L., and Meng, Z.Q. Effects of sulfur dioxide on apoptosis-related gene expressions in lungs from rats. United States: N. p., 2005. Web. doi:10.1016/j.yrtph.2005.09.002.
Bai, J.L., & Meng, Z.Q. Effects of sulfur dioxide on apoptosis-related gene expressions in lungs from rats. United States. doi:10.1016/j.yrtph.2005.09.002.
Bai, J.L., and Meng, Z.Q. Thu . "Effects of sulfur dioxide on apoptosis-related gene expressions in lungs from rats". United States. doi:10.1016/j.yrtph.2005.09.002.
@article{osti_20700879,
title = {Effects of sulfur dioxide on apoptosis-related gene expressions in lungs from rats},
author = {Bai, J.L. and Meng, Z.Q.},
abstractNote = {Sulfur dioxide (SO{sub 2},) is an air pollutant in densely populated areas as well as in areas polluted by coal-fired power plants, smelters, and sulfuric acid factories. In the present study, male Wistar rats were housed in exposure chambers and treated with 14.00 {+-} 1.01, 28.00 {+-} 1.77, and 56.00 {+-} 3.44mg/m{sup 3} SO{sub 2} for 6h/day for 7 days, while control rats were exposed to filtered air in the same condition. The mRNA and protein levels of three apoptosis-related genes (p53 and bax are promoters of apoptosis, whereas bcl-2 is apoptotic suppressor) were analyzed in lungs using a real-time reverse transcription-polymerise chain reaction (real-time RT-PCR) assay and immunohistochemistry method, and caspase-3 activities were detected. The results showed that mRNA levels of p53 and bax were increased in a dose-dependent manner and at the concentrations of 28.00 and 56.00mg/m{sup 3} SO{sub 2} the increases were significant (for p53: 1.23-fold at 28 mg/m{sup 3} and 1.39-fold at 56 mg/m{sup 3}; for bax: 1.77-fold at 28 mg/m{sup 3} and 2.26-fold at 56 mg/m{sup 3}, respectively), while mRNA levels of bcl-2 were decreased significantly (0.78-fold at 28 mg/m{sup 3} and 0.73-fold at 56 mg/m{sup 3}) in lungs of rats exposed to SO{sub 2}. Dose-dependent increase of p53 and bax proteins in the lungs was observed after SO{sub 2} inhalation, while decrease of bcl-2 protein levels was obtained using immunohistochemistry method. Caspase-3 activities were increased in lungs of rats after SO{sub 2} inhalation. These results lead to a conclusion that SO{sub 2}, exposure can change the expression of apoptosis-related genes, and it suggests that SO{sub 2} can induce apoptosis in lung of rat and may have relations with some apoptosis-related diseases. Elucidating the expression patterns of those factors after SO{sub 2} inhalation may be critical to our understanding mechanisms of SO{sub 2} toxicity and helpful for the therapeutic intervention.},
doi = {10.1016/j.yrtph.2005.09.002},
journal = {Regulatory Toxicology and Pharmacology},
number = 3,
volume = 43,
place = {United States},
year = {Thu Dec 01 00:00:00 EST 2005},
month = {Thu Dec 01 00:00:00 EST 2005}
}
  • Apoptosis is a vital mechanism for the regulation of cell turnover and plays a critical role in tissue homeostasis and development of many disease processes. Previous studies have demonstrated the apoptotic effect of tobacco smoke; however, the molecular mechanisms by which tobacco smoke triggers apoptosis remain unclear. In the present study we investigated the effects of tobacco smoke on the induction of apoptosis in the lungs of rats and modulation of nuclear factor-kappa B (NF-{kappa}B) in this process. Exposure of rats to 80 mg/m{sup 3} tobacco smoke significantly induced apoptosis in the lungs. Tobacco smoke resulted in inhibition of NF-{kappa}Bmore » activity, noted by suppression of inhibitor of {kappa}B (I{kappa}B) kinase (IKK), accumulation of I{kappa}B{alpha}, decrease of NF-{kappa}B DNA binding activity, and downregulation of NF-{kappa}B-dependent anti-apoptotic proteins, including Bcl-2, Bcl-xl, and inhibitors of apoptosis. Initiator caspases for the death receptor pathway (caspase 8) and the mitochondrial pathway (caspase 9) as well as effector caspase 3 were activated following tobacco smoke exposure. Tobacco smoke exposure did not alter the levels of p53 and Bax proteins. These findings suggest the role of NF-{kappa}B pathway in tobacco smoke-induced apoptosis.« less
  • In diabetes mellitus (DM), high glucose (HG) and advanced glycation end products (AGEs) are involved in bone quality deterioration. Osteocytes produce sclerostin and receptor activator of nuclear factor-kB ligand (RANKL) and regulate osteoblast and osteoclast function. However, whether HG or AGEs directly affect osteocytes and regulate sclerostin and RANKL production is unknown. Here, we examined the effects of HG, AGE2, and AGE3 on the expression of sclerostin and RANKL and on apoptosis in osteocyte-like MLO-Y4-A2 cells. Treatment of the cells with 22 mM glucose, 100 μg/mL either AGE2 or AGE3 significantly increased the expression of sclerostin protein and mRNA; however, both AGEs,more » but not glucose, significantly decreased the expression of RANKL protein and mRNA. Moreover, treatment of the cells with HG, AGE2, or AGE3 for 72 h induced significant apoptosis. These detrimental effects of HG, AGE2, and AGE3 on sclerostin and RANKL expressions and on apoptosis were antagonized by pretreatment of the cells with 10{sup −8} M human parathyroid hormone (PTH)-(1–34). Thus, HG and AGEs likely suppress bone formation by increasing sclerostin expression in osteocytes, whereas AGEs suppress bone resorption by decreasing RANKL expression. Together, these processes may cause low bone turnover in DM. In addition, HG and AGEs may cause cortical bone deterioration by inducing osteocyte apoptosis. PTH may effectively treat these pathological processes and improve osteocyte function. - Highlights: • AGEs are involved in bone quality deterioration in diabetes mellitus (DM). • AGEs increased sclerostin as well as apoptosis, and decreased RANKL in osteocytes. • The effects of AGEs on osteocyte function were antagonized by human PTH-(1–34). • AGEs may cause low bone turnover and cortical porosity in DM. • PTH may be effective in bone quality deterioration by improving osteocyte function.« less
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  • Highlights: Black-Right-Pointing-Pointer Mechanical stimulation is an important factor for regulation of stem cell fate. Black-Right-Pointing-Pointer Cyclic stretch to human induced pluripotent stem cells activated small GTPase Rho. Black-Right-Pointing-Pointer Rho-kinase activation attenuated pluripotency via inhibition of AKT activation. Black-Right-Pointing-Pointer This reaction could be reproduced only by transfection of dominant active Rho. Black-Right-Pointing-Pointer Rho/ROCK are important molecules in mechanotransduction and control of stemness. -- Abstract: Mechanical stimulation has been shown to regulate the proliferation and differentiation of stem cells. However, the effects of the mechanical stress on the stemness or related molecular mechanisms have not been well determined. Pluripotent stem cells suchmore » as embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are used as good materials for cell transplantation therapy and research of mammalian development, since they can self-renew infinitely and differentiate into various cell lineages. Here we demonstrated that the mechanical stimulation to human iPS cells altered alignment of actin fibers and expressions of the pluripotent related genes Nanog, POU5f1 and Sox2. In the mechanically stimulated iPS cells, small GTPase Rho was activated and interestingly, AKT phosphorylation was decreased. Inhibition of Rho-associated kinase ROCK recovered the AKT phosphorylation and the gene expressions. These results clearly suggested that the Rho/ROCK is a potent primary effector of mechanical stress in the pluripotent stem cells and it participates to pluripotency-related signaling cascades as an upper stream regulator.« less