Perfluorooctane Sulfonate Induces Autophagy-Dependent Apoptosis through Spinster 1-Mediated lysosomal-Mitochondrial Axis and Impaired Mitophagy
| العنوان: | Perfluorooctane Sulfonate Induces Autophagy-Dependent Apoptosis through Spinster 1-Mediated lysosomal-Mitochondrial Axis and Impaired Mitophagy |
|---|---|
| المؤلفون: | Jian Kang, Jun Cao, Xiaofeng Yao, Yuexia Wang, Yufang Ma, Xiance Sun, Min Chen, Shanshan Sha, Liping Jiang |
| المصدر: | Toxicological Sciences. 153:198-211 |
| بيانات النشر: | Oxford University Press (OUP), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Autophagosome, Fluorocarbons, Gene knockdown, Chemistry, ATG5, Autophagy, Mitophagy, Cathepsin D, Apoptosis, PINK1, Hep G2 Cells, Toxicology, Cell biology, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Alkanesulfonic Acids, 030220 oncology & carcinogenesis, Humans, RNA Interference |
| الوصف: | Lysosomal membrane permeabilization (LMP) and subsequently impaired autophagosome degradation was induced in HepG2 cells after treatment with perfluorooctane sulfonate (PFOS) for 24 h in our previous studies. We found that treatment of HepG2 cells with PFOS-induced autophagosome formation at earlier stage (6 h) of treatment in this study. The autophagosome formation inhibitor 3-methyladenine (3-MA) was able to relieve PFOS-induced LMP and release of cathepsin D in HepG2 cells. Knockdown of Spinster 1, a lysosomal membrane permease, attenuated PFOS-induced LMP in HepG2 cells. We proposed that Spinster 1 might work as a specific molecule that linked autophagy with LMP. PFOS-induced collapse of mitochondrial transmembrane potential was cathepsin D and autophagy dependent. Addition of 3-MA relieved PFOS-induced apoptosis, which was evidenced by Hoechst assay, AV/PI staining and caspase-3 activity assay. Inhibition of autophagosome formation by Atg5 siRNA attenuated PFOS-induced apoptosis. Treatment of HepG2 cells with PFOS for 24 h impaired mitophagy, as evidenced by an increase of cells with giant mitochondria and impairment of colocalization of PINK1 with light chain 3. In summary, we report that PFOS induces autophagy-dependent apoptosis in HepG2 cells through the lysosomal-mitochondrial axis and impairment of mitophagy, suggesting that autophagy is a primary target for PFOS toxicity. These findings provide new mechanistic insights into PFOS-induced hepatotoxicity. |
| تدمد: | 1096-0929 1096-6080 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8ab302c73b8b608ef72a0153ff8270eTest https://doi.org/10.1093/toxsci/kfw118Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e8ab302c73b8b608ef72a0153ff8270e |
| قاعدة البيانات: | OpenAIRE |
| ResultId |
1 |
|---|---|
| Header |
edsair OpenAIRE edsair.doi.dedup.....e8ab302c73b8b608ef72a0153ff8270e 822 3 unknown 821.858032226563 |
| PLink |
https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edsair&AN=edsair.doi.dedup.....e8ab302c73b8b608ef72a0153ff8270e&custid=s6537998&authtype=sso |
| FullText |
Array
(
[Availability] => 0
)
|
| Items |
Array
(
[Name] => Title
[Label] => Title
[Group] => Ti
[Data] => Perfluorooctane Sulfonate Induces Autophagy-Dependent Apoptosis through Spinster 1-Mediated lysosomal-Mitochondrial Axis and Impaired Mitophagy
)
Array ( [Name] => Author [Label] => Authors [Group] => Au [Data] => <searchLink fieldCode="AR" term="%22Jian+Kang%22">Jian Kang</searchLink><br /><searchLink fieldCode="AR" term="%22Jun+Cao%22">Jun Cao</searchLink><br /><searchLink fieldCode="AR" term="%22Xiaofeng+Yao%22">Xiaofeng Yao</searchLink><br /><searchLink fieldCode="AR" term="%22Yuexia+Wang%22">Yuexia Wang</searchLink><br /><searchLink fieldCode="AR" term="%22Yufang+Ma%22">Yufang Ma</searchLink><br /><searchLink fieldCode="AR" term="%22Xiance+Sun%22">Xiance Sun</searchLink><br /><searchLink fieldCode="AR" term="%22Min+Chen%22">Min Chen</searchLink><br /><searchLink fieldCode="AR" term="%22Shanshan+Sha%22">Shanshan Sha</searchLink><br /><searchLink fieldCode="AR" term="%22Liping+Jiang%22">Liping Jiang</searchLink> ) Array ( [Name] => TitleSource [Label] => Source [Group] => Src [Data] => <i>Toxicological Sciences</i>. 153:198-211 ) Array ( [Name] => Publisher [Label] => Publisher Information [Group] => PubInfo [Data] => Oxford University Press (OUP), 2016. ) Array ( [Name] => DatePubCY [Label] => Publication Year [Group] => Date [Data] => 2016 ) Array ( [Name] => Subject [Label] => Subject Terms [Group] => Su [Data] => <searchLink fieldCode="DE" term="%220301+basic+medicine%22">0301 basic medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Autophagosome%22">Autophagosome</searchLink><br /><searchLink fieldCode="DE" term="%22Fluorocarbons%22">Fluorocarbons</searchLink><br /><searchLink fieldCode="DE" term="%22Gene+knockdown%22">Gene knockdown</searchLink><br /><searchLink fieldCode="DE" term="%22Chemistry%22">Chemistry</searchLink><br /><searchLink fieldCode="DE" term="%22ATG5%22">ATG5</searchLink><br /><searchLink fieldCode="DE" term="%22Autophagy%22">Autophagy</searchLink><br /><searchLink fieldCode="DE" term="%22Mitophagy%22">Mitophagy</searchLink><br /><searchLink fieldCode="DE" term="%22Cathepsin+D%22">Cathepsin D</searchLink><br /><searchLink fieldCode="DE" term="%22Apoptosis%22">Apoptosis</searchLink><br /><searchLink fieldCode="DE" term="%22PINK1%22">PINK1</searchLink><br /><searchLink fieldCode="DE" term="%22Hep+G2+Cells%22">Hep G2 Cells</searchLink><br /><searchLink fieldCode="DE" term="%22Toxicology%22">Toxicology</searchLink><br /><searchLink fieldCode="DE" term="%22Cell+biology%22">Cell biology</searchLink><br /><searchLink fieldCode="DE" term="%2203+medical+and+health+sciences%22">03 medical and health sciences</searchLink><br /><searchLink fieldCode="DE" term="%22030104+developmental+biology%22">030104 developmental biology</searchLink><br /><searchLink fieldCode="DE" term="%220302+clinical+medicine%22">0302 clinical medicine</searchLink><br /><searchLink fieldCode="DE" term="%22Alkanesulfonic+Acids%22">Alkanesulfonic Acids</searchLink><br /><searchLink fieldCode="DE" term="%22030220+oncology+%26+carcinogenesis%22">030220 oncology & carcinogenesis</searchLink><br /><searchLink fieldCode="DE" term="%22Humans%22">Humans</searchLink><br /><searchLink fieldCode="DE" term="%22RNA+Interference%22">RNA Interference</searchLink> ) Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => Lysosomal membrane permeabilization (LMP) and subsequently impaired autophagosome degradation was induced in HepG2 cells after treatment with perfluorooctane sulfonate (PFOS) for 24 h in our previous studies. We found that treatment of HepG2 cells with PFOS-induced autophagosome formation at earlier stage (6 h) of treatment in this study. The autophagosome formation inhibitor 3-methyladenine (3-MA) was able to relieve PFOS-induced LMP and release of cathepsin D in HepG2 cells. Knockdown of Spinster 1, a lysosomal membrane permease, attenuated PFOS-induced LMP in HepG2 cells. We proposed that Spinster 1 might work as a specific molecule that linked autophagy with LMP. PFOS-induced collapse of mitochondrial transmembrane potential was cathepsin D and autophagy dependent. Addition of 3-MA relieved PFOS-induced apoptosis, which was evidenced by Hoechst assay, AV/PI staining and caspase-3 activity assay. Inhibition of autophagosome formation by Atg5 siRNA attenuated PFOS-induced apoptosis. Treatment of HepG2 cells with PFOS for 24 h impaired mitophagy, as evidenced by an increase of cells with giant mitochondria and impairment of colocalization of PINK1 with light chain 3. In summary, we report that PFOS induces autophagy-dependent apoptosis in HepG2 cells through the lysosomal-mitochondrial axis and impairment of mitophagy, suggesting that autophagy is a primary target for PFOS toxicity. These findings provide new mechanistic insights into PFOS-induced hepatotoxicity. ) Array ( [Name] => ISSN [Label] => ISSN [Group] => ISSN [Data] => 1096-0929<br />1096-6080 ) Array ( [Name] => URL [Label] => Access URL [Group] => URL [Data] => <link linkTarget="URL" linkTerm="https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8ab302c73b8b608ef72a0153ff8270e" linkWindow="_blank">https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e8ab302c73b8b608ef72a0153ff8270e</link><br /><link linkTarget="URL" linkTerm="https://doi.org/10.1093/toxsci/kfw118" linkWindow="_blank">https://doi.org/10.1093/toxsci/kfw118</link> ) Array ( [Name] => Copyright [Label] => Rights [Group] => Cpyrght [Data] => OPEN ) Array ( [Name] => AN [Label] => Accession Number [Group] => ID [Data] => edsair.doi.dedup.....e8ab302c73b8b608ef72a0153ff8270e ) |
| RecordInfo |
Array
(
[BibEntity] => Array
(
[Languages] => Array
(
[0] => Array
(
[Text] => Undetermined
)
)
[PhysicalDescription] => Array
(
[Pagination] => Array
(
[PageCount] => 14
[StartPage] => 198
)
)
[Subjects] => Array
(
[0] => Array
(
[SubjectFull] => 0301 basic medicine
[Type] => general
)
[1] => Array
(
[SubjectFull] => Autophagosome
[Type] => general
)
[2] => Array
(
[SubjectFull] => Fluorocarbons
[Type] => general
)
[3] => Array
(
[SubjectFull] => Gene knockdown
[Type] => general
)
[4] => Array
(
[SubjectFull] => Chemistry
[Type] => general
)
[5] => Array
(
[SubjectFull] => ATG5
[Type] => general
)
[6] => Array
(
[SubjectFull] => Autophagy
[Type] => general
)
[7] => Array
(
[SubjectFull] => Mitophagy
[Type] => general
)
[8] => Array
(
[SubjectFull] => Cathepsin D
[Type] => general
)
[9] => Array
(
[SubjectFull] => Apoptosis
[Type] => general
)
[10] => Array
(
[SubjectFull] => PINK1
[Type] => general
)
[11] => Array
(
[SubjectFull] => Hep G2 Cells
[Type] => general
)
[12] => Array
(
[SubjectFull] => Toxicology
[Type] => general
)
[13] => Array
(
[SubjectFull] => Cell biology
[Type] => general
)
[14] => Array
(
[SubjectFull] => 03 medical and health sciences
[Type] => general
)
[15] => Array
(
[SubjectFull] => 030104 developmental biology
[Type] => general
)
[16] => Array
(
[SubjectFull] => 0302 clinical medicine
[Type] => general
)
[17] => Array
(
[SubjectFull] => Alkanesulfonic Acids
[Type] => general
)
[18] => Array
(
[SubjectFull] => 030220 oncology & carcinogenesis
[Type] => general
)
[19] => Array
(
[SubjectFull] => Humans
[Type] => general
)
[20] => Array
(
[SubjectFull] => RNA Interference
[Type] => general
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Perfluorooctane Sulfonate Induces Autophagy-Dependent Apoptosis through Spinster 1-Mediated lysosomal-Mitochondrial Axis and Impaired Mitophagy
[Type] => main
)
)
)
[BibRelationships] => Array
(
[HasContributorRelationships] => Array
(
[0] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Jian Kang
)
)
)
[1] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Jun Cao
)
)
)
[2] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Xiaofeng Yao
)
)
)
[3] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Yuexia Wang
)
)
)
[4] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Yufang Ma
)
)
)
[5] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Xiance Sun
)
)
)
[6] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Min Chen
)
)
)
[7] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Shanshan Sha
)
)
)
[8] => Array
(
[PersonEntity] => Array
(
[Name] => Array
(
[NameFull] => Liping Jiang
)
)
)
)
[IsPartOfRelationships] => Array
(
[0] => Array
(
[BibEntity] => Array
(
[Dates] => Array
(
[0] => Array
(
[D] => 13
[M] => 07
[Type] => published
[Y] => 2016
)
)
[Identifiers] => Array
(
[0] => Array
(
[Type] => issn-print
[Value] => 10960929
)
[1] => Array
(
[Type] => issn-print
[Value] => 10966080
)
[2] => Array
(
[Type] => issn-locals
[Value] => edsair
)
[3] => Array
(
[Type] => issn-locals
[Value] => edsairFT
)
)
[Numbering] => Array
(
[0] => Array
(
[Type] => volume
[Value] => 153
)
)
[Titles] => Array
(
[0] => Array
(
[TitleFull] => Toxicological Sciences
[Type] => main
)
)
)
)
)
)
)
|
| IllustrationInfo |