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STAT3 signaling promotes cardiac injury by upregulating NCOA4-mediated ferritinophagy and ferroptosis in high-fat-diet fed mice
In this study, we found that oleic acid/palmitic acid (OA/PA) increased the level of ferroptotic events including iron and ROS accumulation, upregulation of PTGS2 mRNA and protein levels, reduced SOD and GSH levels, and significant mitochondrial damage in H9C2 cells, which could be reversed by the ferroptosis inhibitor ferrostatin-1 (Fer-1). Intriguingly, we found that the autophagy inhibitor 3-methyladenine mitigated OA/PA-induced ferritin downregulation, iron overload and ferroptosis. OA/PA increased the protein level of NCOA4. Knockdown of NCOA4 by SiRNA partly reversed the reduction in ferritin, mitigated iron overload...
Source: Free Radical Biology and Medicine - March 20, 2023 Category: Biology Authors: Mengying Zhu Lulu Peng Shengqi Huo Dewei Peng Junyi Gou Wei Shi Jingwen Tao Tao Jiang Yue Jiang Qian Wang Bingyu Huang Lintong Men Sheng Li Jiagao Lv Li Lin Source Type: research

Caveolin-1 alleviates acetaminophen-induced vascular oxidative stress and inflammation in non-alcoholic fatty liver disease
In conclusion, our findings confirmed that CAV1 exerts a protective effect against vascular injury by inhibiting oxidative stress and inflammation through the PKC/MAPK pathway. Therefore, restoration of CAV1 may have clinical benefits in reducing APAP-induced vascular damage in NAFLD patients.PMID:36596386 | DOI:10.1016/j.freeradbiomed.2022.12.095
Source: Free Radical Biology and Medicine - January 3, 2023 Category: Biology Authors: Dongdong Fu Shuai Wu Xiangfu Jiang Tingyu You Yu Li Jiao Xin Xiaowen Feng Jiagen Wen Yan Huang Chengmu Hu Source Type: research

NLRP3 inflammasome mediate palmitate-induced endothelial dysfunction
This study aimed to investigate the role of NLRP3 (NOD-like receptor pyrin domain containing-3) inflammasome in FFA induced endothelial dysfunction.Main methodsHUVECs were transfected with NLRP3 siRNA and then stimulated with LPS and palmitate. C57 BL/6J mice transfected with NLRP3 Lenti-Virus were fed with a high-fat diet (HFD). The levels of NLRP3 inflammasome, AMPKα (AMP-activated protein kinase), endothelial nitric oxide synthase (eNOS) and the activity of the insulin signal pathway, in endothelial cells were determined via Western blotting. Endothelial function was determined by measuring the level of endothelium-dep...
Source: Life Sciences - November 7, 2019 Category: Biology Source Type: research

The role of the BMP4/Smad1 signaling pathway in mesangial cell proliferation: A possible mechanism of diabetic nephropathy
This study explored the role of the BMP4/Smad1 signaling pathway in mesangial matrix expansion during the process of diabetic nephropathy.Main methodsDiabetic rats were induced by high-fat feeding followed by an intraperitoneal injection of streptozotocin. Glomerular lesions were examined. Immunohistochemical analysis was performed in order to identify BMP4/Smad1 signaling proteins (BMP4, ALK3, and Smad1) and mesangial ECM proteins (Col1 and Col4) in kidney tissue. Cell proliferation and the expression of BMP4, Smad1 and Col4 were determined in cultured mesangial cells exposed to high glucose. The specific regulatory role ...
Source: Life Sciences - January 29, 2019 Category: Biology Source Type: research

High circulatory leptin mediated NOX-2-peroxynitrite-miR21 axis activate mesangial cells and promotes renal inflammatory pathology in nonalcoholic fatty liver disease
Publication date: July 2018Source: Redox Biology, Volume 17Author(s): Firas Alhasson, Ratanesh Kumar Seth, Sutapa Sarkar, Diana A. Kimono, Muayad S. Albadrani, Diptadip Dattaroy, Varun Chandrashekaran, Geoffrey I. Scott, Samir Raychoudhury, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, Saurabh ChatterjeeAbstractHigh circulatory insulin and leptin followed by underlying inflammation are often ascribed to the ectopic manifestations in non-alcoholic fatty liver disease (NAFLD) but the exact molecular pathways remain unclear. We have shown previously that CYP2E1-mediated oxidative stress and circulating leptin in NAFLD...
Source: Redox Biology - July 11, 2018 Category: Biology Source Type: research

SOCS2 exacerbates myocardial injury induced by ischemia/reperfusion in diabetic mice and H9c2 cells through inhibiting the JAK-STAT-IGF-1 pathway
This study aimed to investigate potential candidates and molecular mechanisms of myocardial ischemia/reperfusion (I/R) injury (MIRI) in type 2 diabetes mellitus. Main methods Type 2 diabetic and myocardial I/R mouse models were established with a high fat-diet (HFD) for 24weeks and subjecting to global ischemia/reperfusion for 1h/3h, respectively. Microarray analysis was applied to screen differentially expressed genes (DEGs) in the hearts of these mice. Moreover, H9c2 cells were treated with high glucose (HG) and/or hypoxia and reoxygenation (H/R). Subsequently, the expression of suppressor of cytokine signaling 2 (SOCS2)...
Source: Life Sciences - September 8, 2017 Category: Biology Source Type: research