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Source: Free Radical Biology and Medicine
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Total 199 results found since Jan 2013.
Nrf2 depletion in the context of loss-of-function Keap1 leads to mitolysosome accumulation
Free Radic Biol Med. 2023 Sep 13:S0891-5849(23)00627-5. doi: 10.1016/j.freeradbiomed.2023.09.009. Online ahead of print.ABSTRACTTranscription factor nuclear factor erythroid 2 p45-related factor 2 (Nrf2) is the principal determinant of the cellular redox homeostasis, contributing to mitochondrial function, integrity and bioenergetics. The main negative regulator of Nrf2 is Kelch-like ECH associated protein 1 (Keap1), a substrate adaptor for Cul3/Rbx1 ubiquitin ligase, which continuously targets Nrf2 for ubiquitination and proteasomal degradation. Loss-of-function mutations in Keap1 occur frequently in lung cancer, leading ...
Source: Free Radical Biology and Medicine - September 15, 2023 Category: Biology Authors: Sharadha Dayalan Naidu Plamena R Angelova Elena V Knatko Chiara Leonardi Miroslav Novak Laureano de la Vega Ian G Ganley Andrey Y Abramov Albena T Dinkova-Kostova Source Type: research
Oxidative stress and inflammation are mediated via aryl hydrocarbon receptor signalling in idiopathic membranous nephropathy
Free Radic Biol Med. 2023 Jul 12:S0891-5849(23)00543-9. doi: 10.1016/j.freeradbiomed.2023.07.014. Online ahead of print.ABSTRACTMembranous nephropathy (MN) patients are diagnosed by the presence of phospholipase A2 receptor (PLA2R) before they progress to renal failure. However, the subepithelium-like immunocomplex deposit-mediated downstream molecular pathways are poorly understood. The aryl hydrocarbon receptor (AHR), NF-ƙB and Nrf2 pathways play central roles in the pathogenesis and progression of chronic kidney disease. However, their mutual effects on MN require further examination. Thus, we investigated the effect o...
Source: Free Radical Biology and Medicine - July 14, 2023 Category: Biology Authors: Yan-Ni Wang Hua Miao Xiao-Yong Yu Yan Guo Wei Su Fei Liu Gang Cao Ying-Yong Zhao Source Type: research
Evaluation of the role of Sigma 1 receptor and Cullin3 in retinal photoreceptor cells
Free Radic Biol Med. 2023 Jun 14:S0891-5849(23)00496-3. doi: 10.1016/j.freeradbiomed.2023.06.010. Online ahead of print.ABSTRACTSigma 1 receptor (Sig1R), a pluripotent modulator of cell survival, is neuroprotective in models of retinal degeneration when activated by the high-affinity, high-specificity ligand (+)-pentazocine ((+)-PTZ). The molecular mechanisms of Sig1R-mediated retinal neuroprotection are under investigation. We previously reported that the antioxidant regulatory transcription factor Nrf2 may be involved in Sig1R-mediated retinal photoreceptor cell (PRC) rescue. Cullin 3 (Cul3) is a component of the Nrf2-Ke...
Source: Free Radical Biology and Medicine - June 16, 2023 Category: Biology Authors: Jing Wang Shannon R Barwick Haiyan Xiao Sylvia B Smith Source Type: research
AMPK negatively regulates RANKL-induced osteoclast differentiation by controlling oxidative stress
This study aimed to clarify the mechanistic connection between AMPK and osteoclast differentiation, and the potential role of AMPK in the anti-resorptive effects of several phytochemicals. We found that receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL)-induced osteoclast differentiation, osteoclastic gene expression, and activation of mitogen-activated protein kinase (MAPK) and NF-κB were promoted in cells transfected with AMPK siRNA. AMPK knockdown led to defective synthesis of heme oxygenase-1, an antioxidant enzyme, and the upstream mediator, nuclear factor erythroid-2-related factor 2. Furthermore, ...
Source: Free Radical Biology and Medicine - June 3, 2023 Category: Biology Authors: Miori Tanaka Hirofumi Inoue Nobuyuki Takahashi Mariko Uehara Source Type: research
Metformin protects against retinal ischemia/reperfusion injury through AMPK-mediated mitochondrial fusion
This study aims to evaluate the protective effect of metformin against retinal I/R injury and its underlying mechanism. I/R induced reduction in retina thickness and cell number in ganglion cell layer, and metformin alleviated I/R-induced retinal injury. Both retinal I/R and simulated ischemia/reperfusion (SIR) in R28 cells down-regulated expression of mitochondrial fusion protein Mfn2 and OPA1, which led to mitochondrial fission. Metformin also alleviated damage in R28 cells, and reversed the alteration in Mfn2 and OPA1, mitochondrial fission and mitochondrial membrane potential (MMP) disruption-induced by I/R or SIR as w...
Source: Free Radical Biology and Medicine - May 30, 2023 Category: Biology Authors: Kun Zhang Tao Wang Gui-Feng Sun Jin-Xing Xiao Li-Ping Jiang Fang-Fang Tou Xin-Hui Qu Xiao-Jian Han Source Type: research
P2X7R/AKT/mTOR signaling mediates high glucose-induced decrease in podocyte autophagy
We examined the expression of all purinergic receptors in the renal cortex and found that only purinergic P2X7 receptor (P2X7R) expression was significantly increased in the renal cortex of wild-type diabetic mice and that the P2X7R protein partially co-localized with podocytes. Compared with P2X7R(-/-) non-diabetic mice, P2X7R(-/-) diabetic mice showed stable expression of the podocyte marker protein podocin in the renal cortex. The renal expression of microtubule associated protein 1A/1B light chain 3 (LC-3II) in wild-type diabetic mice was significantly lower than in wild-type controls, whereas the expression of LC-3II ...
Source: Free Radical Biology and Medicine - May 28, 2023 Category: Biology Authors: Cheng Qian Jiayue Lu Xiajing Che Lulin Min Minzhou Wang Ahui Song Renhua Lu Leyi Gu Kewei Xie Source Type: research
Astragaloside IV attenuates podocyte apoptosis through ameliorating mitochondrial dysfunction by up-regulated Nrf2-ARE/TFAM signaling in diabetic kidney disease
In this study, using molecular docking we found that Astragaloside IV (AS-IV), an active ingredient from traditional formula of Huangqi decoction (HQD), exerted a higher potential to promote Nrf2 escape from Keap1-Nrf2 interaction via competitively bind to amino acid sites in Keap1. When podocyte exposed to high glucose (HG) stimulation, mitochondrial morphological alterations and podocyte apoptosis were presented and accompanied by Nrf2 and mitochondrial transcription factor A (TFAM) downregulation. Mechanistically, HG promoted a decrease in mitochondria-specific electron transport chain (ETC) complexes, ATP synthesis and...
Source: Free Radical Biology and Medicine - April 8, 2023 Category: Biology Authors: Qian Shen Ji Fang Hengjiang Guo Xue Su Bingbing Zhu Xingmei Yao Yunman Wang Aili Cao Hao Wang Li Wang Source Type: research
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
