دورية أكاديمية
Acute Endoplasmic Reticulum Stress Suppresses Hepatic Gluconeogenesis by Stimulating MAPK Phosphatase 3 Degradation
العنوان: | Acute Endoplasmic Reticulum Stress Suppresses Hepatic Gluconeogenesis by Stimulating MAPK Phosphatase 3 Degradation |
---|---|
المؤلفون: | Xiaohua Huang, Heng Zhu, Wei Lu, Lei Cao, Zhengfeng Fang, Lianqiang Che, Yan Lin, Shengyu Xu, Yong Zhuo, Lun Hua, Xuemei Jiang, Mengmeng Sun, De Wu, Bin Feng |
المصدر: | International Journal of Molecular Sciences, Vol 24, Iss 21, p 15561 (2023) |
بيانات النشر: | MDPI AG, 2023. |
سنة النشر: | 2023 |
المجموعة: | LCC:Biology (General) LCC:Chemistry |
مصطلحات موضوعية: | DILI, ER stress, PERK, MKP-3, gluconeogenesis, Biology (General), QH301-705.5, Chemistry, QD1-999 |
الوصف: | Drug-induced liver injury (DILI) is a widespread and harmful disease, and is closely linked to acute endoplasmic reticulum (ER) stress. Previous reports have shown that acute ER stress can suppress hepatic gluconeogenesis and even leads to hypoglycemia. However, the mechanism is still unclear. MAPK phosphatase 3 (MKP-3) is a positive regulator for gluconeogenesis. Thus, this study was conducted to investigate the role of MKP-3 in the suppression of gluconeogenesis by acute ER stress, as well as the regulatory role of acute ER stress on the expression of MKP-3. Results showed that acute ER stress induced by tunicamycin significantly suppressed gluconeogenesis in both hepatocytes and mouse liver, reduced glucose production level in hepatocytes, and decreased fasting blood glucose level in mice. Additionally, the protein level of MKP-3 was reduced by acute ER stress in both hepatocytes and mouse liver. Mkp-3 deficiency eliminated the inhibitory effect of acute ER stress on gluconeogenesis in hepatocytes. Moreover, the reduction effect of acute ER stress on blood glucose level and hepatic glucose 6-phosphatase (G6pc) expression was not observed in the liver-specific Mkp-3 knockout mice. Furthermore, activation of protein kinase R-like ER kinase (PERK) decreased the MKP-3 protein level, while inactivation of PERK abolished the reduction effect of acute ER stress on the MKP-3 protein level in hepatocytes. Taken together, our study suggested that acute ER stress could suppress hepatic gluconeogenesis by stimulating MKP-3 degradation via PERK, at least partially. Thus, MKP-3 might be a therapeutic target for DILI-related hypoglycemia. |
نوع الوثيقة: | article |
وصف الملف: | electronic resource |
اللغة: | English |
تدمد: | 1422-0067 1661-6596 |
Relation: | https://www.mdpi.com/1422-0067/24/21/15561; https://doaj.org/toc/1661-6596; https://doaj.org/toc/1422-0067 |
DOI: | 10.3390/ijms242115561 |
URL الوصول: | https://doaj.org/article/10f3a22d64744ff284565fab6908ef71 |
رقم الأكسشن: | edsdoj.10f3a22d64744ff284565fab6908ef71 |
قاعدة البيانات: | Directory of Open Access Journals |
تدمد: | 14220067 16616596 |
---|---|
DOI: | 10.3390/ijms242115561 |