Tumour necrosis factor-α promotes liver ischaemia-reperfusion injury through the PGC-1α/Mfn2 pathway
| العنوان: | Tumour necrosis factor-α promotes liver ischaemia-reperfusion injury through the PGC-1α/Mfn2 pathway |
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| المؤلفون: | Wenbo Ke, Hong Zhou, Hong Luo, Bin Yang, Yongzhong Wu, Qi Zhou, Qichang Zheng, Yong Zhang, Jun Li, Yu Guo |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | Blackwell Publishing Ltd, 2014. |
| سنة النشر: | 2014 |
| مصطلحات موضوعية: | Male, medicine.medical_specialty, Necrosis, MFN2, Mitochondria, Liver, Biology, liver, mitofusion2, Cell Line, GTP Phosphohydrolases, tumour necrosis factor alpha, Mitochondrial Proteins, Rats, Sprague-Dawley, ischaemia-reperfusion injury, Ischemia, Internal medicine, medicine, Animals, Humans, chemistry.chemical_classification, Reactive oxygen species, urogenital system, Tumor Necrosis Factor-alpha, Liver Diseases, Membrane Proteins, Cell Biology, Original Articles, medicine.disease, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Endocrinology, chemistry, peroxisome proliferator–activated receptor-γ co-activator-1α, Cell culture, Apoptosis, Reperfusion Injury, Hepatocytes, Molecular Medicine, Tumor necrosis factor alpha, medicine.symptom, Signal transduction, Reperfusion injury, Signal Transduction, Transcription Factors |
| الوصف: | Tumour necrosis factor (TNF)-α has been considered to induce ischaemia-reperfusion injury (IRI) of liver which is characterized by energy dysmetabolism. Peroxisome proliferator–activated receptor-γ co-activator (PGC)-1α and mitofusion2 (Mfn2) are reported to be involved in the regulation of mitochondrial function. However, whether PGC-1α and Mfn2 form a pathway that mediates liver IRI, and if so, what the underlying involvement is in that pathway remain unclear. In this study, L02 cells administered recombinant human TNF-α had increased TNF-α levels and resulted in down-regulation of PGC-1α and Mfn2 in a rat liver IRI model. This was associated with hepatic mitochondrial swelling, decreased adenosine triphosphate (ATP) production, and increased levels of reactive oxygen species (ROS) and alanine aminotransferase (ALT) activity as well as cell apoptosis. Inhibition of TNF-α by neutralizing antibody reversed PGC-1α and Mfn2 expression, and decreased hepatic injury and cell apoptosis both in cell culture and in animals. Treatment by rosiglitazone sustained PGC-1α and Mfn2 expression both in IR livers, and L02 cells treated with TNF-α as indicated by increased hepatic mitochondrial integrity and ATP production, reduced ROS and ALT activity as well as decreased cell apoptosis. Overexpression of Mfn2 by lentiviral-Mfn2 transfection decreased hepatic injury in IR livers and L02 cells treated with TNF-α. However, there was no up-regulation of PGC-1α. These findings suggest that PGC-1α and Mfn2 constitute a regulatory pathway, and play a critical role in TNF-α-induced hepatic IRI. Inhibition of the TNF-α or PGC-1α/Mfn2 pathways may represent novel therapeutic interventions for hepatic IRI. |
| اللغة: | English |
| تدمد: | 1582-4934 1582-1838 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e603168175e935ba6cc87d4ac96d280e http://europepmc.org/articles/PMC4196661 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....e603168175e935ba6cc87d4ac96d280e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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