USP47 promotes apoptosis in rat myocardial cells after ischemia/reperfusion injury via NF‐κB activation

Abstract

An increasing number of studies have associated nuclear factor‐κB (NF‐κB) activation to the progression of myocardial infarction (MI). Multiple members of the ubiquitin‐specific protease (USP) family regulate the NF‐κB signaling pathway. This study attempted to investigate the function and underlying mechanism of USP family members in MI. Monocytes were isolated from peripheral blood samples of MI and healthy control, and the expression of several USP family members and NF‐κB was examined. After USP47 knockdown or overexpression, cell apoptosis, related protein levels, and NF‐κB promoter activity were measured. We found that USP47 and NF‐κB expression was significantly increased in MI, and USP47 was positively correlated with NF‐κB. In a rat H9c2 myocardial cell ischemia/reperfusion (I/R) injury model, USP47 expression was increased in a time‐dependent manner. USP47 knockdown decreased I/R injury‐induced apoptosis, with increased survivin and cytoplasmic NF‐κB and decreased cleaved caspase‐3 and nuclear NF‐κB. USP47‐induced apoptosis was potently counteracted by the NF‐κB inhibitor, and cytoplasmic NF‐κB was increased and nuclear NF‐κB was decreased. Luciferase reporter showed that USP47 promotes NF‐κB promoter activity. These results suggested that USP47 expression may be correlated with MI progression. USP47 knockdown attenuated myocardial cell I/R injury by inhibiting apoptosis.

Nuciferine from Nelumbo nucifera Gaertn. attenuates isoproterenol‐induced myocardial infarction in Wistar rats

“…Similarly, treatment Groups IV, V, and VI showed a well‐arranged sinusoid with hepatic venule groups, with disrupted hepatic venules, lack of a nucleus in hepatocytes revealing necrosis, infiltration of degenerated hepatocytes, and inflammation in Group III (Figure 6A). Fibrosis is the progression of the inflammation after the post‐MI 50 Groups I, V, and VI showed the lack of collagen accumulation. Group V showed mild thickening of the outer layer of epicardium ( tunica adventitia ), whereas Group VI showed inflammatory damage on the myocardial tissue ( tunica media ) with fibrosis (Figure 6B).…”

Role of Ubiquitin-Specific Peptidase 47 in Cancers and Other Diseases

“…Therefore, USP47 expression may be related to the progression of myocardial infarction. Downregulating USP47 reduced myocardial ischemia-reperfusion injury by inhibiting apoptosis (Hu et al, 2020).…”

“…At the post-transcriptional level, many non-coding RNAs are involved in regulating USP47 expression. USP47 is the target protein of miR-204-5p, and high miR-204-5p expression leads to down-regulation of USP47 expression, thereby inhibiting proliferation of gastric cancer and ovarian cancer cells (Zhang et al, 2015;Hu et al, 2020). USP47 is also a target protein of miR-188-5p in CRC.…”

“…The ubiquitin system is involved in inflammation, as the deubiquitinases A20, BRCC3, and USP50 (Lopez-Castejon and Edelmann, 2016). USP47 has been proven to be related to the nuclear localization of NF-κB (Hu et al, 2020). When the canonical NF-κB pathway was stimulated, IκBα was phosphorylated, promoting its β-TrCP-mediated ubiquitinylation and degradation, thereby releasing NF-κB into nucleus.…”

Administration of USP7 inhibitor P22077 inhibited cardiac hypertrophy and remodeling in Ang II-induced hypertensive mice

“…Ubiquitin (Ub)-specific proteases (UPSs), the largest subfamily of DUBs, remove Ub chains from the substrates to regulate the stability, activity and subcellular localization of the target substrates ( Lee et al, 2013 ; Eletr and Wilkinson, 2014 ). Increasing evidence has demonstrated that DUBs have a crucial role in cardiovascular diseases, such as cardiac hypertrophy, myocardial infarction, atrial fibrillation, heart failure, and others ( Liu et al, 2016 ; Bi et al, 2020a ; Bi et al, 2020b ; Hu et al, 2021 ). USP7 (also called Herpesvirus-associated ubiquitin-specific protease, HAUSP), the first identified DUBs, participated in cell proliferation, DNA damage response, tumourigenesis, inflammation, and apoptosis by regulating its substrates, such as MDM2/p53, PTEN, FOXO4, NF-κB, and other target proteins ( Khoronenkova et al, 2012 ; Smits and Freire, 2016 ; Xu et al, 2022 ).…”