For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
10
views
23
references
 Top references
cited by
3
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      466
      similar
       All similar
      • Record: found
      • Abstract: found
      • Article: not found

      Effect of Di-(2-ethylhexyl)-phthalate on Sphingolipid Metabolic Enzymes in Rat Liver

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Di-(2-ethylhexyl)-phthalate (DEHP), the most widely utilized industrial plastizer and a ubiquitous environmental contaminant, can act on peroxisome proliferators-activated nuclear hormone receptor family (PPAR) isoforms. To understand the contribution of sphingolipid metabolism to DEHP-induced hepatotoxicity, effect of DEHP exposure on activities of sphingolipid metabolic enzymes in rat liver was investigated. DEHP (250, 500 or 750 mg/kg) was administered to the rats through oral gavage daily for 28 days. The activities of acidic and alkaline ceramidases were slightly increased in 250 mg/kg DEHP-administered rat livers and significantly elevated in 500 mg/kg DEHP-administered ones, although the level of 750 mg/kg DEHP-administered ones was not increased. Neutral ceramidase, acidic and neutral sphingomyelinases, sphingomyeline synthase and ceramide syhthase were not changed at all by DEHP exposure. Therefore, acidic and alkaline ceramidases might play important roles in DEHP-induced hepatotoxicity.

          Related collections

          Most cited references23

          • Record: found
          • Abstract: not found
          • Article: not found

          A rapid method of total lipid extraction and purification.

          E G BLIGH, W. Dyer (1959)
          Article 0 comments Cited 1746 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Functions of ceramide in coordinating cellular responses to stress.

            Y Hannun (1996)
            Sphingolipid metabolites participate in key events of signal transduction and cell regulation. In the sphingomyelin cycle, a number of extracellular agents and insults (such as tumor necrosis factor, Fas ligands, and chemotherapeutic agents) cause the activation of sphingomyelinases, which act on membrane sphingomyelin and release ceramide. Multiple experimental approaches suggest an important role for ceramide in regulating such diverse responses as cell cycle arrest, apoptosis, and cell senescence. In vitro, ceramide activates a serine-threonine protein phosphatase, and in cells it regulates protein phosphorylation as well as multiple downstream targets [such as interleukin converting enzyme (ICE)-like proteases, stress-activated protein kinases, and the retinoblastoma gene product] that mediate its distinct cellular effects. This spectrum of inducers of ceramide accumulation and the nature of ceramide-mediated responses suggest that ceramide is a key component of intracellular stress response pathways.
            Article 0 comments Cited 185 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              De novo ceramide regulates the alternative splicing of caspase 9 and Bcl-x in A549 lung adenocarcinoma cells. Dependence on protein phosphatase-1.

              Charles E. Chalfant, Kristin Rathman, Ryan L Pinkerman … (2002)
              Previous studies have demonstrated that several splice variants are derived from both the caspase 9 and Bcl-x genes in which the Bcl-x splice variant, Bcl-x(L) and the caspase 9 splice variant, caspase 9b, inhibit apoptosis in contrast to the pro-apoptotic splice variants, Bcl-x(s) and caspase 9. In a recent study, we showed that ceramide induces the dephosphorylation of SR proteins, a family of protein factors that regulate alternative splicing. In this study, the regulation of the alternative processing of pre-mRNA of both caspase 9 and Bcl-x(L) was examined in response to ceramide. Treatment of A549 lung adenocarcinoma cells with cell-permeable ceramide, D-e-C(6) ceramide, down-regulated the levels of Bcl-x(L) and caspase 9b mRNA and immunoreactive protein with a concomitant increase in the mRNA and immunoreactive protein levels of Bcl-x(s) and caspase 9 in a dose- and time-dependent manner. Pretreatment with calyculin A (5 nm), an inhibitor of protein phosphatase-1 (PP1) and protein phosphatase 2A (PP2A) blocked ceramide-induced alternative splicing in contrast to okadaic acid (10 nm), a specific inhibitor of PP2A at this concentrations in cells, demonstrating a PP1-mediated mechanism. A role for endogenous ceramide in regulating the alternative splicing of caspase 9 and Bcl-x was demonstrated using the chemotherapeutic agent, gemcitabine. Treatment of A549 cells with gemcitabine (1 microm) increased ceramide levels 3-fold via the de novo sphingolipid pathway as determined by pulse labeling experiments and inhibition studies with myriocin (50 nm), a specific inhibitor of serine palmitoyltransferase (the first step in de novo synthesis of ceramide). Treatment of A549 cells with gemcitabine down-regulated the levels of Bcl-x(L) and caspase 9b mRNA with a concomitant increase in the mRNA levels of Bcl-x(s) and caspase 9. Again, inhibitors of ceramide synthesis blocked this effect. We also demonstrate that the change in the alternative splicing of caspase 9 and Bcl-x occurred prior to apoptosis following treatment with gemcitabine. Furthermore, doses of D-e-C(6) ceramide that induce the alternative splicing of both caspase 9 and Bcl-x-sensitized A549 cells to daunorubicin. These data demonstrate a role for protein phosphatases 1 (PP1) and endogenous ceramide generated via the de novo pathway in regulating this mechanism. This is the first report on the dynamic regulation of RNA splicing of members of the Bcl-2 and caspase families in response to regulators of apoptosis.
              Article 0 comments Cited 67 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Journal ID (nlm-ta): Toxicol Res
                Journal ID (iso-abbrev): Toxicol Res
                Journal ID (publisher-id): ksot
                Title: Toxicological Research
                Publisher: The Korean Society of Toxicology
                ISSN (Print): 1976-8257
                Publication date (Print): September 2011
                Volume: 27
                Issue: 3
                Pages: 185-190
                Affiliations
                [1 ]Laboratories of Pharmacology, Pusan National University, Busan 609-735, Korea
                [2 ]Molecular Toxicology, College of Pharmacy (BK21 Project) and Longevity Life Science and Technology Institutes, Pusan National University, Busan 609-735, Korea
                [3 ]Department of Food Science & Technology, Tongmyong University, Busan 608-711, Korea
                Author notes
                Correspondence to: Dong-Soon Im, Laboratory of Pharmacology, College of Pharmacy, Pusan National University, San 30, Jang-Jundong, Geum-Jung-gu, Busan 609-735, Korea E-mail: imds@ 123456pusan.ac.kr
                Article
                Publisher ID: toxicr-27-185
                DOI: 10.5487/TR.2011.27.3.185
                PMC ID: 3834377
                PubMed ID: 24278571
                SO-VID: 9e0a0b96-9912-42e2-9541-f4561f79aace
                Copyright © Copyright ©2011, The Korean Society of Toxicology
                History
                Date received : 07 April 2011
                Date revision received : 14 July 2011
                Date accepted : 11 August 2011
                Categories
                Subject: Articles

                Keywords: di-(2-ethylhexyl)-phthalate,sphingosine,sphingomyelinase,ceramidase,liver,sphingomyelin synthase,ceramide synthase
                Data availability:
                Keywords: di-(2-ethylhexyl)-phthalate, sphingosine, sphingomyelinase, ceramidase, liver, sphingomyelin synthase, ceramide synthase

                Comments

                Comment on this article

                scite_

                Similar content466

                See all similar

                Cited by3

                See all cited by

                Most referenced authors270

                See all reference authors