ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2022
Caffeine alleviates acute liver injury by inducing the expression of NEDD4L and deceasing GRP78 level via ubiquitination.
Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 12 citations in OpenAlex.
- Article
- Intestinal Epithelial-Derived USP13 Alleviates Colonic Inflammation by Suppressing GRP78-mediated Endoplasmic Reticulum Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- [RecombinantNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- NEDD4 and NEDD4L: Ubiquitin Ligases Closely Related to Digestive Diseases.Biomolecules · 2024Review
- Caffeine and neonatal acute kidney injury.Pediatric nephrology (Berlin, Germany) · 2024Review
- Uridine diphosphate glucuronosyltransferase 1A1 prevents the progression of liver injury.World journal of gastroenterology · 2024Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAcute liver injury is liver cell injury that occurs rapidly in a short period of time. Caffeine has been shown to maintain hepatoprotective effect with an unclear mechanism. Endoplasmic reticulum stress (ERS) has significant effects in acute liver injury. Induction of GRP78 is a hallmark of ERS. Whether or not caffeine's function is related to GRP78 remains to be explored.
methodsAcute liver injury model was established by LPS-treated L02 cells and in vivo administration of LPS/D-Gal in mice. Caffeine was pre-treated in L02 cells or mice. Gene levels was determined by real-time PCR and western blot. Cell viability was tested by CCK-8 assay and cell apoptosis was tested by flow cytometry. The interaction of GRP78 and NEDD4L was determined by Pull-down and co-immunoprecipitation (Co-IP) assay. The ubiquitination by NEDD4L on GRP78 was validated by in vitro ubiquitination assay.
resultsCaffeine protected liver cells against acute injury induced cell apoptosis and ERS both in vitro and in vivo. Suppression of GRP78 could block the LPS-induced cell apoptosis and ERS. NEDD4L was found to interact with GRP78 and ubiquitinate its lysine of 324 site directly. Caffeine treatment induced the expression of NEDD4L, resulting in the ubiquitination and inhibition of GRP78.
conclusionCaffeine mitigated the acute liver injury by stimulating NEDD4L expression, which inhibited GRP78 expression via ubiquitination at its K324 site. Low dose of caffeine could be a promising therapeutic treatment for acute liver injury.
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