Perfluorononanoic acid-induced apoptosis in rat spleen involves oxidative stress and the activation of caspase-independent death pathway
Fang, X; Feng, Y; Wang, J; Dai, J
HERO ID
2919316
Reference Type
Journal Article
Year
2010
Language
English
PMID
| HERO ID | 2919316 |
|---|---|
| In Press | No |
| Year | 2010 |
| Title | Perfluorononanoic acid-induced apoptosis in rat spleen involves oxidative stress and the activation of caspase-independent death pathway |
| Authors | Fang, X; Feng, Y; Wang, J; Dai, J |
| Journal | Toxicology |
| Volume | 267 |
| Issue | 1-3 |
| Page Numbers | 54-59 |
| Abstract | Perfluoroalkyl acid (PFAA)-induced apoptosis has been reported in many cell types. However, minimal information on its mode of action is available. This study explored the possible involvement of apoptotic signaling pathways in a nine-carbon-chain length PFAA-perfluorononanoic acid (PFNA)-induced splenocyte apoptosis. After a 14-day exposure to PFNA, rat spleens showed dose-dependent levels of apoptosis. The production of pro-inflammatory and anti-inflammatory cytokines was significantly increased and decreased, respectively. However, protein levels of tumor necrosis factor receptor 1 (TNFR1), fas-associated protein with death domain (FADD), caspase 8 and caspase 3, which are involved in inflammation-related and caspase-dependent apoptosis, were discordant. Peroxisome proliferator-activated receptors alpha (PPARalpha) and PPARgamma genes expression was up-regulated in rats treated with 3 or 5 mg/kg/day of PFNA, and the level of hydrogen peroxide (H2O2) increased concurrently in rats treated with the highest dose. Moreover, superoxide dismutase (SOD) activity and Bcl-2 protein levels were dramatically decreased in spleens after treatment with 3 and 5 mg/kg/day of PFNA. However, protein levels of Bax were unchanged. Apoptosis-inducing factor (AIF), an initiator of caspase-independent apoptosis, was significantly increased in all PFNA-dosed rats. Thus, oxidative stress and the activation of a caspase-independent apoptotic signaling pathway contributed to PFNA-induced apoptosis in rat splenocytes. |
| Doi | 10.1016/j.tox.2009.10.020 |
| Pmid | 19878704 |
| Wosid | WOS:000274588700008 |
| Url | https://search.proquest.com/docview/746076075?accountid=171501 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |
| Keyword | Environment Abstracts; Toxicology Abstracts; Tumor necrosis factor receptors; Oxidative stress; Hydrogen peroxide; Bax protein; Bcl-2 protein; Superoxide dismutase; Caspase-3; FADD protein; Fas-associated protein; Proteins; Signal transduction; Splenocytes; tumor necrosis factor receptor 1; Cytokines; Apoptosis-inducing factor; Mortality; Inflammation; Caspase-8; Peroxisome proliferator-activated receptors; Apoptosis; ENA 02:Toxicology & Environmental Safety; X 24490:Other |