Suppression of Grb2 expression improved hepatic steatosis, oxidative stress, and apoptosis induced by palmitic acid in vitro partly through insulin signaling alteration
| Autor: | Changzhi Song, Guangzhou Wu, Wenzhang Zha, Guangjun Zhou, Xiang-Ming Mu, Xiangxiang Shan, Jian Zhu, Guan Sun, Rengen Fan, Yan Chen, Yufeng Miao, Zhengqiang Wan |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
medicine.medical_specialty
Cell Survival Glucose uptake Palmitic Acid Apoptosis In Vitro Techniques Carbohydrate metabolism medicine.disease_cause Palmitic acid chemistry.chemical_compound Internal medicine medicine Humans Insulin Protein kinase B GRB2 Adaptor Protein biology Caspase 3 Fatty liver Hep G2 Cells Cell Biology General Medicine Lipid Metabolism medicine.disease Genes bcl-2 Fatty Liver Oxidative Stress Insulin receptor bcl-2 Homologous Antagonist-Killer Protein Endocrinology Gene Expression Regulation chemistry biology.protein Steatosis Oxidative stress Signal Transduction Developmental Biology |
| Zdroj: | In Vitro Cellular & Developmental Biology - Animal. 49:576-582 |
| ISSN: | 1543-706X 1071-2690 |
| DOI: | 10.1007/s11626-013-9646-9 |
| Popis: | In this study, we aimed to study the role of growth factor receptor-bound protein 2 (Grb2) in palmitic acid-induced steatosis and other "fatty liver" symptoms in vitro. HepG2 cells, with or without stably suppressed Grb2 expression, were incubated with palmitic acid for 24 h to induce typical clinical "fatty liver" features, including steatosis, impaired glucose metabolism, oxidative stress, and apoptosis. MTT and Oil Red O assays were applied to test cell viability and fat deposition, respectively. Glucose uptake assay was used to evaluate the glucose utilization of cells. Quantitative polymerase chain reaction and Western blot were used to measure expressional changes of key markers of insulin signaling, lipid/glucose metabolism, oxidative stress, and apoptosis. After 24-h palmitic acid induction, increased fat accumulation, reduced glucose uptake, impaired insulin signaling, enhanced oxidative stress, and increased apoptosis were observed in HepG2 cells. Suppression of Grb2 in HepG2 significantly reduced fat accumulation, improved glucose metabolism, ameliorated oxidative stress, and restored the activity of insulin receptor substrate-1/Akt and MEK/ERK pathways. In addition, Grb2 deficiency attenuated hepatic apoptosis shown by reduced activation of caspase-3 and fluorescent staining. Modulation of Bcl-2 and Bak1 also contributed to reduced apoptosis. In conclusion, suppression of Grb2 expression in HepG2 cells improved hepatic steatosis, glucose metabolism, oxidative stress, and apoptosis induced by palmitic acid incubation partly though modulating the insulin signaling pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full text from SpringerLink