JOURNAL OF PROTEOME RESEARCH
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2021
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IF 4.466
Peng Ma,Zijing Wang,Yisa Wang,Biyu Hou,Jialin Sun,He Tian,Bowen Li,Guanghou Shui,Xiuying Yang,Xinyu Yang,Guifen Qiang,Chong Wee Liew,Guanhua Du
Once protein synthesis is excessive or misfolded protein becomes aggregated, which eventually overwhelms the capacity of the endoplasmic reticulum (ER), a state named ER stress would be reached. ER stress could affect many tissues, especially the liver, in which nonalcoholic fatty liver disease, liver steatosis, etc. have been reported relative. However, there is still a lack of systematic insight into ER stress in the liver, which can be obtained by integrating metabolomics and transcriptomics of the tissue. Here, tunicamycin was utilized to induce ER stress in C57BL/6N mice. Microarray and untargeted metabolomics were performed to identify the genes and metabolites significantly altered in liver tissues. Surprisingly, apart from the predictable unfolded protein response, liver lipid, arginine, and proline metabolisms were affirmed to be related to ER stress. Also, the ketone body metabolism changed most prominently in response to ER stress, with few studies backing. What is more, succinate receptor 1 (Sucnr1) may be a novel marker and therapeutical target of liver ER stress. In this study, the combination of the metabolome and transcriptome provided reliable information about liver pathological processes, including key relative pathways, potential markers, and targets involved in ER stress of the liver.
研究领域:
分子生物学
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生物化学
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系统生物学
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肝病学
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产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACOLOGY
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2022
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IF 5.195
Xiangxiang Li,Jing Zhou,Zhuozhou Hu,Liang Han,Wenyang Zhao,Tongyu Wu,Chun Li,Jingjing Liu,Jia Kang,Xinping Chen
Obesity, a global epidemic chronic metabolic disease , urgently demands novel therapies. As an antimalarial drug , quinacrine has not been reported for its anti-obesity effect to our knowledge. This study aimed to explore the ability of quinacrine to attenuate obesity. In an in vitro adipogenic model, quinacrine exhibited an outstanding suppression on adipogenesis of 3T3-L1 cells, mainly by activating the AMPK (Adenosine 5′-monophosphate (AMP)-activated protein kinase) signaling pathway to regulate preadipocytes differentiation and lipid accumulation. In addition, C57BL/6N female mice were fed with high-fat diet and high-fructose water for 14 weeks to establish an obesity model, followed by oral administration of quinacrine or orlistat . After 9 weeks of treatment, quinacrine significantly reduced the body weight and energy intake, ameliorated the impaired glucose tolerance and restored the homeostasis of serum lipids. Also, quinacrine improved lipid profile and optimized the expression of AMPK signaling pathway related proteins in livers and adipose tissues of obese mice . Quinacrine reverses obesity through activating AMPK phosphorylation to down-regulate adipogenesis, along with lowering the risk of type 2 diabetes and atherosclerosis . It should be a novel application for the treatment of obesity and its associated diseases.
研究领域:
药理学
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代谢性疾病
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分子生物学
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内分泌学
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产品关联
DOI
PubMed
高影响因子
TOXICOLOGY MECHANISMS AND METHODS
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2021
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IF 2.987
Lirui Hou,Fang Liu,Chong Zhao,Lihong Fan,Hongbo Hu,Shutao Yin
Oxytetracycline (OTC) and Quinocetone (QCT) are antimicrobials, whose residues have been found in food and environment. These two are sometimes used simultaneously in livestock and aquaculture, potentially resulting in the simultaneous consumption of multi-antimicrobials by consumers. However, the combined toxic effects of this phenomenon have yet to be addressed. Since the liver is a major target of both OTC and QCT, we tested their hepatotoxic effect using both cell cultures and animal models. Results showed that the QCT (5–25 μM) or OTC (20–100 μM) treatments alone caused dose-dependent reductions in cell numbers, while their combination strongly further enhanced inhibitory effects. Mechanistically, the combination enhanced the generation of reactive oxygen species (ROS) and activated mitochondrial cell death pathways. It also showed that the combination of OTC (800 mg/kg, i.g., 5d) and QCT (5000 mg/kg, i.g., 5d) resulted in significantly enhanced liver toxicity in C57BL/6N mice, the serum alanine transaminase (ALT) and aspartate transaminase (AST) were significantly increased by the OTC/QCT. These findings indicate the necessity of considering the combined toxicity of these two antimicrobials in safety assessments.
研究领域:
毒理学
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药理学
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细胞生物学
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动物科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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