Data · collection · 2015
Melatonin protects hepatocytes against bile acid-induced mitochondrial oxidative stress via the AMPK-SIRT3-SOD2 pathway
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Mitochondrial oxidative damage is hypothesized to contribute to the pathogenesis of chronic cholestatic liver diseases.
Description
Melatonin, an indolamine synthesized in the pineal gland, shows a wide range of physiological functions, and is under clinical investigation for expanded applications. Melatonin has demonstrated efficient protective effects against various types of oxidative damage in the liver system.
This study investigates the protective effects of melatonin pretreatment on glycochenodeoxycholic acid (GCDCA)-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. Melatonin markedly decreased mitochondrial ROS (mROS) production in L02 cells treated with 100 μM GCDCA, and inhibited GCDCA-stimulated cytotoxicity. Notably, melatonin exerted its hepatoprotective effects by upregulating sirtuin 3 (SIRT3) activity and its expression level, thus regulating superoxide dismutase 2 (SOD2) acetylation and inhibiting the production of mROS induced by GCDCA.
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Moreover, siRNA targeting SIRT3 blocked the melatonin-mediated elevation in mitochondrial function by inhibiting SIRT3/SOD2 signaling. Importantly, melatonin-activated SIRT3 activity was completely abolished by AMP-activated, alpha 1 catalytic subunit (AMPK) siRNA transfection. Similar results were obtained in rat with bile duct ligation or BDL.
In summary, our findings indicate that melatonin is a novel hepatoprotective small molecule that functions by elevating SIRT3, stimulating SOD2 activity, and suppressing mitochondrial oxidative stress at least through AMPK, and that SIRT3 may be of therapeutic value in liver cell protection for GCDCA-induced hepatotoxicity.
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Where it is published
- Repository landing page tandf.figshare.com/collections/Melatonin_protects_hepatocytes_against_bile_acid_i… ↗
landing page · from DataCite
- Repository landing page tandf.figshare.com/collections/Melatonin_protects_hepatocytes_against_bile_acid_i… ↗
landing page · from DataCite
- DOI doi.org/10.6084/m9.figshare.c.2115062 ↗
DOI / persistent id · from DataCite
- DOI doi.org/10.6084/m9.figshare.c.2115062.v1 ↗
DOI / persistent id · from DataCite
Documentation and papers
Catalogue records · 4
- DataCite API api.datacite.org/dois/10.6084/m9.figshare.c.2115062.v1 ↗
metadata API · from DataCite
- DataCite API api.datacite.org/dois/10.6084/m9.figshare.c.2115062 ↗
metadata API · from DataCite
- DataCite Commons commons.datacite.org/doi.org/10.6084/m9.figshare.c.2115062.v1 ↗
catalogue entry · from DataCite
- DataCite Commons commons.datacite.org/doi.org/10.6084/m9.figshare.c.2115062 ↗
catalogue entry · from DataCite
Topics
- Stated by source
- Biological sciences · Biological sciences · Chemical sciences · Chemical sciences · Clinical medicine · Clinical medicine
- From keywords
- Cancer · Cancer · Chemistry · Chemistry · Life Sciences · Life Sciences
Provenance · 2 source records, 19 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| DataCite | 10.6084/m9.figshare.c.2115062 | 14 d ago | JSON v1 |
| DataCite | 10.6084/m9.figshare.c.2115062.v1 | 14 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · DataCite | connector:datacite@1.0.0 | /data/attributes/rightsList |
| concepts[disease].local:disease:cancer | mapping · DataCite | vocabulary-mapper@1.0.0 | keywords['Cancer'] |
| concepts[disease].local:disease:cancer | mapping · DataCite | vocabulary-mapper@1.0.0 | keywords['Cancer'] |
| concepts[field].fos:biological-sciences | source · DataCite | connector:datacite@1.0.0 | |
| concepts[field].fos:biological-sciences | source · DataCite | connector:datacite@1.0.0 | |
| concepts[field].fos:chemical-sciences | source · DataCite | connector:datacite@1.0.0 | |
| concepts[field].fos:chemical-sciences | source · DataCite | connector:datacite@1.0.0 | |
| concepts[field].fos:clinical-medicine | source · DataCite | connector:datacite@1.0.0 | |
| concepts[field].fos:clinical-medicine | source · DataCite | connector:datacite@1.0.0 | |
| concepts[field].local:field:chemistry | mapping · DataCite | vocabulary-mapper@1.0.0 | keywords['Chemistry'] |
| concepts[field].local:field:chemistry | mapping · DataCite | vocabulary-mapper@1.0.0 | keywords['Chemistry'] |
| concepts[field].local:field:life-sciences | mapping · DataCite | vocabulary-mapper@1.0.0 | keywords['Biological Sciences'] |
| concepts[field].local:field:life-sciences | mapping · DataCite | vocabulary-mapper@1.0.0 | keywords['Biological Sciences'] |
| created_date | source · DataCite | connector:datacite@1.0.0 | |
| description | source · DataCite | connector:datacite@1.0.0 | /data/attributes/descriptions |
| license | source · DataCite | connector:datacite@1.0.0 | /data/attributes/rightsList |
| publication_date | source · DataCite | connector:datacite@1.0.0 | /data/attributes/dates |
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