HYPERTENSION RESEARCH
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2019
·Vol. 43
·期 3
·168-177
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IF 3.217
Bi Hai-Lian,Zhang Yun-Long,Yang Jie,Shu Qing,Yang Xiao-Lei,Yan Xiao,Chen Chen,Li Zhi,Li Hui-Hua
Atrial fibrillation (AF) is the most common human arrhythmia in clinical practice and may be promoted by atrial inflammation and fibrosis. Ubiquitination is an important posttranslational modification process that is reversed by deubiquitinating enzymes (DUBs). DUBs play critical roles in modulating the degradation, activity, trafficking, and recycling of substrates. However, less research has focused on the role of DUBs in AF. Here, we investigated the effect of ubiquitin C-terminal hydrolase 1 (UCHL1), an important DUB, on the development of AF induced by angiotensin II (Ang II). Male wild-type mice were treated with the UCHL1 inhibitor LDN57444 (LDN) at a dose of 40 μg/kg and infused with Ang II (2000 ng/kg/min) for 3 weeks. Our results showed that Ang II-infused wild-type (WT) mice had higher systolic blood pressure and an increased incidence and duration of AF. Conversely, this effect was attenuated in LDN-treated mice. Moreover, the administration of LDN significantly reduced Ang II-induced left atrial dilation, fibrosis, inflammatory cell infiltration, and reactive oxygen species (ROS) production. Mechanistically, LDN treatment inhibited the activation of multiple signaling pathways (the AKT, ERK1/2, HIF-1α, and TGF-β/smad2/3 pathways) and the expression of CX43 protein in atrial tissues compared with that in vehicle-treated control mice. Overall, our study identified UCHL1 as a novel regulator that contributes to Ang II-induced AF and suggests that the administration of LDN may represent a potential therapeutic approach for treating hypertensive AF.
研究领域:
心脏病学
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药理学
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分子生物学
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PubMed
高影响因子
BIOCHEMICAL PHARMACOLOGY
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2026
·
IF 6.5
Tiantian Wan,Xiya Wang,Xue Mei,Shubin Guo
Ubiquitin C-terminal hydrolase 1 (UCHL1), a critical deubiquitinating enzyme (DUB), cleaves ubiquitin/polyubiquitin chains from substrate proteins and has been shown to promote oxidative stress and inflammatory response. However, UCHL1′s precise role in sepsis-induced liver injury (SILI) pathogenesis remains unknown. Here, we show elevated UCHL1 in cecal ligation puncture (CLP)-induced livers and lipopolysaccharide (LPS)-treated bone marrow-derived macrophages (BMDMs). Deficiency or pharmacological inhibition of UCHL1 with LDN-57444 (LDN) conferred protection against SILI by inhibiting oxidative stress and M1 macrophage polarization through targeting the degradation of glucose-6-phosphate isomerase (Gpi) and suppressing Gpi–mediated glycolysis. In contrast, the overexpression of Gpi reversed the inhibitory effects of UCHL1 deficiency on sepsis. Bone marrow transplantation combined with in vitro studies further showed that myeloid UCHL1 deficiency similarly improved SILI through suppression of Gpi stabilization and glycolysis. Hence, targeting UCHL1 in myeloid cells emerged as a protective strategy against SILI, highlighting its potential as a novel therapeutic avenue for patient care.
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高影响因子
Biotechnology Journal
·
2023
·
IF 4.7
Yan-Fei Shen,Ming-Jie Liu,Zhu Long,Xiaobang Shi,Meng-Lu Liu
High-throughput western blot (WB) analysis can be used to obtain more consistent, comparable, and informative data from precious samples and materials with extremely limited availability, such as various age-related, subtype-specific human induced neurons (hiNs). In this study, p-toluenesulfonic acid (PTSA), an odorless tissue fixative, was used to inactivate horseradish peroxidase (HRP) and develop a high-throughput WB method. PTSA-treated blots demonstrated rapid and efficient HRP inactivation without detectable protein loss or epitope damage. With a brief PTSA treatment (1 min at room temperature [RT]) before every subsequent probing, 10 dopaminergic hiN proteins could be sequentially, sensitively, and specifically detected in the blot. The resulting WB data confirmed the age-associated and neuron-specific features of hiNs and revealed a significant reduction in two Parkinson's disease-associated proteins, UCHL1 and GAP43, in normal aging dopaminergic neurons. Overall, this study developed a unique and high-efficiency WB analysis method for capturing robust and useful data from limited, precious samples. Graphical and Lay Summary Inactivation of horseradish peroxidase (HRP) facilitates multiple reprobing of a single blot to sequentially detect different proteins instead of rerunning several gels and blots. In this study, the authors demonstrate that p-toluenesulfonic acid (PTSA) inactivates HRP rapidly and efficiently, allowing simple, flexible, and high-efficiency western blot (WB) analysis of diverse proteins on a single blot for age-related, subtype-specific human induced neurons. The results imply the promising potential of PTSA as an excellent and user-friendly HRP-inactivating reagent for novel high-throughput WB analysis, with considerable importance for research on limited, precious samples.
研究领域:
神经科学
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分子生物学
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蛋白质组学
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）