Senp1

OBJECTIVES: Astragaloside IV (AST IV) and ligustrazine (Lig), the main ingredients of Astragali Radix and Chuanxiong Rhizoma respectively, have demonstrated significant benefits in treatment of cerebral ischemia -reperfusion injury (CIRI); however, the mechanisms underlying its benificial effects remain unclear. SUMO-1ylation and deSUMO-2/3ylation of dynamin-related protein 1 (Drp1) results in mitochondrial homeostasis imbalance following CIRI, which subsequently aggravates cell damage...

BACKGROUND: The protein annexin A6 (AnxA6) is involved in numerous membrane-related biological processes including cell migration and invasion by interacting with other proteins. The dysfunction of AnxA6, including protein expression abundance change and imbalance of post-translational modification, is tightly related to multiple cancers. Herein we focus on the biological function of AnxA6 SUMOylation in hepatocellular carcinoma (HCC) progression. METHODS: The modification sites of AnxA6 SUMOylation were identified by LC-MS/MS and amino acid site mutation...

Oxidative stress is employed to depict a series of responses detrimental to normal cellular functions resulting from an imbalance between intracellular oxidants, mainly reactive oxygen species and antioxidant defenses. Oxidative stress often contributes to the development of various diseases, including cancer, cardiovascular diseases, and neurodegenerative diseases. In this process, the relationship between small ubiquitin-like modifier (SUMO) and oxidative stress has garnered significant attention, with its posttranslational modification (PTM) frequently serving as a marker of oxidative stress status...

Liver sinusoidal endothelial cells (LSECs) have an important role in hepatic ischemia‑reperfusion injury (I/R), but the specific molecular mechanism of action is unknown. LSEC proliferation is regulated and fenestration is maintained via the Sentrin/SUMO‑specific protease 1 (SENP1)/hypoxia‑inducible factor‑1α (HIF‑1α) signaling axis under hypoxic conditions. In the present study, a hypoxia‑reoxygenation (H‑R) injury model was established using mouse LSECs to explore the relationship between SENP1 and H‑R injury in vitro , and the specific underlying mechanism was identified, revealing new targets for the clinical attenuation of hepatic I/R injury...

Acting as a cysteine protease, small ubiquitin-like modifier (SUMO)/sentrin-specific protease1 (SENP1) involved in multiple physiological and pathological processes through processing the precursor SUMO protein into mature form and deSUMOylating target protein. It has been reported that SENP1 is highly expressed and plays a carcinogenic role in various cancers. In this paper, we mainly explore the function and mechanism of SENP1 in tumor cell proliferation, apoptosis, invasion, metastasis, stemness, angiogenesis, metabolism and drug resistance...

In a previous study, we discovered that the level of lnc-TSPAN12 was significantly elevated in hepatocellular carcinoma (HCC) and correlated with a low survival rate. However, the function and mechanism of lnc-TSPAN12 in modulating epithelial-mesenchymal transition (EMT) and metastasis in HCC remains poorly understood. This study demonstrates that lnc-TSPAN12 positively influences migration, invasion, and EMT of HCC cells in vitro and promotes hepatic metastasis in vivo. The modification of N6-methyladenosine, driven by METTL3, is essential for the stability of lnc-TSPAN12, which may partially contribute to the upregulation of lnc-TSPAN12...

Defects of human trophoblast cells may induce miscarriage (abnormal early embryo loss), which is generally regulated by lncRNAs. Ferroptosis is a newly identified iron-dependent programmed cell death. Hypoxia is an important and unavoidable feature in mammalian cells. However, whether hypoxia might induce trophoblast cell ferroptosis and then induce miscarriage, as well as regulated by a lncRNA, was completely unknown. In this work, we discovered at the first time that hypoxia could result in ferroptosis of human trophoblast cells and then induce miscarriage...

As a common complication of Crohn's disease (CD), the mechanism underlying CD intestinal fibrosis remains unclear. Studies have shown that epithelial-mesenchymal transition (EMT) is a key step in the development of intestinal fibrosis in CD. It is currently known that the long non-coding RNA (lncRNA) MSC-AS1 plays an important role in regulating the secretion of inflammatory mediators and EMT; however, its role in intestinal fibrosis remains unclear. MSC-AS1 was significantly upregulated in the CD intestinal tissue and intestinal tissue of mice treated with 2,4,6-trinitrobenzenesulfonic acid...

The ε4 allele of apolipoprotein E (APOE4) and aging are the major risk factors for Alzheimer's disease (AD). SUMOylation is intimately linked to the development of AD and the aging process. However, the SUMOylation status in APOE4 mice has not been uncovered. In this study, we investigated SENP1 and SUMOylation changes in the brains of aged APOE3 and APOE4 mice, aiming to understand their potential impact on mitochondrial metabolism and their contribution to cellular senescence in APOE4 mice. Concurrently, SUMO1-conjugated protein levels decreased, while SUMO2/3-conjugated protein levels increased relatively with the aging of APOE4 mice...

A 60-day study was carried out to determine the effect of dietary selenium nanoparticles (SeNP) on growth, digestive enzymes, and health status of Asian seabass ( Lates calcarifer , 46.5 ± 0.2 g) juveniles reared in high saline water (48 ppt). Five levels of SeNP were added to a basal diet (45% protein, 15% lipid), including control (0), 0.5 (SeNP0.5), 1.0 (SeNP1), 2 (SeNP2), and 4 (SeNP4) mg SeNP kg-1 diet. Fish were stocked into fifteen 2,000 L tanks (50 fish tank-1 ) filled with 1,800 L sand-filtered seawater (26...

Pathological cardiac hypertrophy is the leading cause of heart failure and has an extremely complicated pathogenesis. TEA domain transcription factor 1 (TEAD1) is recognized as an important transcription factor that plays a key regulatory role in cardiovascular disease. This study aimed to explore the role of TEAD1 in cardiac hypertrophy and to clarify the regulatory role of small ubiquitin-like modifier (SUMO)-mediated modifications. First, the expression level of TEAD1 in patients with heart failure, mice, and cardiomyocytes is investigated...

Head and neck squamous cell carcinoma (HNSCC) is currently one of the most common malignancies with a poor prognosis worldwide. Meanwhile, small ubiquitin‑like modifier (SUMO) specific peptidase 1 (SENP1) was associated with ferroptosis. However, the specific functions and underlying mechanisms of action of SENP1 in ferroptosis and tumor progression of HNSCC remain to be established. The findings of the present study implicated a novel ferroptosis pathway in the initiation and progression of HNSCC, providing new functional targets to guide future therapy...

Pancreatic β-cells respond to metabolic stress by upregulating insulin secretion, however the underlying mechanisms remain unclear. Here we show, in β-cells from overweight humans without diabetes and mice fed a high-fat diet for 2 days, insulin exocytosis and secretion are enhanced without increased Ca2+ influx. RNA-seq of sorted β-cells suggests altered metabolic pathways early following high fat diet, where we find increased basal oxygen consumption and proton leak, but a more reduced cytosolic redox state...

Nicotinamide adenine dinucleotide (NAD+ ) is an essential element in cellular metabolism that regulates fundamental biological processes. Growing evidence suggests that a decline in NAD+ is a common pathological factor in various diseases and aging. However, its role in airway epithelial barrier function in response to asthma remains underexplored. The current study aims to explore the efficacy of restoring cellular NAD+ concentration through supplementation with the NAD+  precursor, nicotinamide mononucleotide (NMN), in the treatment of allergic asthma and to investigate the role of SIRT3 in mediating the effects of NAD+  precursors...

Hepatic ischemia/reperfusion injury (HIRI) represents a prevalent pathophysiological process that imposes a substantial economic burden in clinical practice, especially in liver surgery. Sentrin-specific protease 1 (SENP1) is a crucial enzyme involved in the regulation of SUMOylation, and is related to various diseases. However, the role of SENP1 in HIRI remains unexplored. Here, we confirmed that SENP1 actively participated in modulating the oxidative damage induced by HIRI. Notably, SENP1 functioned by maintaining mitochondrial homeostasis...

Recurrent implantation failure (RIF) patients exhibit poor endometrial receptivity and abnormal decidualization with reduced effectiveness and exposure to progesterone, which is an intractable clinical problem. However, the associated molecular mechanisms remain elusive. We found that EH homeodomain 1 (EHD1) expression was abnormally elevated in RIF and linked to aberrant endometrial decidualization. Here we show that EHD1 overexpressed in human endometrial stromal cells (HESCs) significantly inhibited progesterone receptor (PGR) transcriptional activity and the responsiveness to progesterone...

Glutamine synthetase (GS) is a crucial enzyme involved in de novo synthesis of glutamine and participates in several biological processes, including nitrogen metabolism, nucleotide synthesis, and amino acid synthesis. Post-translational modification makes GS more adaptable to the needs of cells, and acetylation modification of GS at double sites has attracted considerable attention. Despite very intensive research, how SUMOylation affects GS activity at a molecular level remains unclear. Here, we report that previously undiscovered GS SUMOylation which is deficient mutant K372R of GS exhibits more bluntness under glutamine starvation...

BACKGROUND: Excessive inflammation is the main cause of treatment failure in neonatal pneumonia (NP). CCCTC-binding factor (CTCF) represents an important node in various inflammatory diseases. In the present study, we tried to clarify the function and underlying molecular mechanism of CTCF on an in vitro cellular model of NP, which was generated by simulating the human lung fibroblast cell line WI-38 with lipopolysaccharide (LPS). METHODS: The SUMOylation level and protein interaction were verified by Co-immunoprecipitation assay...

Our previous report established that RUNX family transcription factor 1 (RUNX1) promotes proliferation of mouse retinal microvascular endothelial cells (mRMECs) and exacerbates diabetic retinopathy (DR). However, the mechanism behind the upregulation of RUNX1 remains unclear. This study aims to investigate the possible correlation between histone SUMOylation and RUNX1 in DR, as well as the involved molecules. A mouse model of diabetes was induced by streptozotocin (STZ). These mice had increased retinal thickness and elevated production of inflammatory cytokines...

Gliomas are the most common primary brain tumors in adults. Although they exist in different malignant stages, most gliomas are clinically challenging because of their infiltrative growth patterns and inherent relapse tendency with increased malignancy. Epigenetic alterations have been suggested to be an important factor for glioma genesis. Using mRNA probe hybridization, we identified SUMO-specific protease 1 (SENP1) as the most significantly upregulated SUMOylation regulator in glioma. Moreover, SENP1 was overexpressed in gliomas and predicted poor prognoses...