Positive feedback loop involving AMPK and CLYBL acetylation links metabolic rewiring and inflammatory responses.

Metabolic rewiring underlies effective macrophages defense to respond disease microenvironment. However, the underlying mechanisms driving metabolic rewiring to enhance macrophage effector functions remain unclear. Here, we demonstrated that the metabolic reprogramming in inflammatory macrophages depended on the acetylation of CLYBL, a citramalyl-CoA lyase, at lysine 154 (K154), and blocking CLYBL-K154 acetylation restricted the release of pro-inflammatory factors.

GLP-1: A Prospective Guardian for Comprehensive Myocardial Perfusion.

Objective: To investigate the role of glucagon-like peptide 1 (GLP-1) in myocardial perfusion, focusing on its effects on coronary microcirculation and cardiovascular outcomes.

Methods: Review of foundational research and large-scale clinical trials, including Cardiovascular Outcome Trials (CVOTs), examining the cardiovascular effects of GLP-1. Systematic analysis of trial data to assess the impact of GLP-1 therapy on myocardial infarction, composite cardiovascular events, and stroke incidence.

Erratum to "WWP2 protects against sepsis-induced cardiac injury through inhibiting cardiomyocyte ferroptosis".

[This corrects the article DOI: 10.2478/jtim-2024-0004.].

WWP2 protects against sepsis-induced cardiac injury through inhibiting cardiomyocyte ferroptosis.

Background And Objectives: Cardiac injury plays a critical role in contributing to the mortality associated with sepsis, a condition marked by various forms of programmed cell deaths. Previous studies hinted at the WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) involving in heart failure and endothelial injury. However, the precise implications of WWP2 in sepsis-induced cardiac injury, along with the underlying mechanisms, remain enigmatic.

Cathepsin D Attenuates the Proliferation of Vascular Smooth Muscle Cells Induced by the AGE/RAGE Pathway by Suppressing the ERK Signal.

Background: In this study, we aimed to clarify the role and mechanism by which Cathepsin D (CTSD) mediates the advanced glycation end products (AGEs)-induced proliferation of vascular smooth muscle cells (VSMCs).

Methods: We conducted a Western blotting assay and co-immunoprecipitation assay to detect the expression of target proteins and the interaction between different proteins. Cell Counting Kit-8 (CCK-8) assay and 5- ethynyl-2'-deoxyuridine (EdU) were used to evaluate the proliferation.

Atorvastatin rescues vascular endothelial injury in hypertension by WWP2-mediated ubiquitination and degradation of ATP5A.

As a widely used lipid-lowering drug in clinical practice, atorvastatin is widely recognized for its role in protecting vascular endothelium in the cardiovascular system. However, a clear mechanistic understanding of its action is lacking. Here, we found that atorvastatin counteracted angiotensin II-induced vascular endothelial injury in mice with hypertension.

The role of SMURFs in non-cancerous diseases.

The ubiquitin-proteasome system is a crucial mechanism for regulating protein levels in cells, with substrate-specific E3 ubiquitin ligases serving as an integral component of this system. Among these ligases are SMAD-specific E3 ubiquitin-protein ligase 1 (SMURF1) and SMAD-specific E3 ubiquitin-protein ligase 2 (SMURF2), which belong to the neural precursor cell-expressed developmentally downregulated 4 (NEDD4) subfamily of Homologous to E6-AP COOH terminus (HECT)-type E3 ligases. As E3 ligases, SMURFs have critical functions in regulating the stability of multiple proteins, thereby maintaining physiological processes such as cell migration, proliferation, and apoptosis.

α-myosin heavy chain lactylation maintains sarcomeric structure and function and alleviates the development of heart failure.

The sarcomeric interaction of α-myosin heavy chain (α-MHC) with Titin is vital for cardiac structure and contraction. However, the mechanism regulating this interaction in normal and failing hearts remains unknown. Lactate is a crucial energy substrate of the heart.

Down-regulation of WWP2 aggravates Type 2 diabetes mellitus-induced vascular endothelial injury through modulating ubiquitination and degradation of DDX3X.

Background: Endothelial injury caused by Type 2 diabetes mellitus (T2DM) is considered as a mainstay in the pathophysiology of diabetic vascular complications (DVCs). However, the molecular mechanism of T2DM-induced endothelial injury remains largely unknown. Here, we found that endothelial WW domain-containing E3 ubiquitin protein ligase 2 (WWP2) act as a novel regulator for T2DM-induced vascular endothelial injury through modulating ubiquitination and degradation of DEAD-box helicase 3 X-linked (DDX3X).

Deacetylation of Septin4 by SIRT2 (Silent Mating Type Information Regulation 2 Homolog-2) Mitigates Damaging of Hypertensive Nephropathy.

Background: Hypertension can lead to podocyte damage and subsequent apoptosis, eventually resulting in glomerulosclerosis. Although alleviating podocyte apoptosis has clinical significance for the treatment of hypertensive nephropathy, an effective therapeutic target has not yet been identified. The function of septin4, a proapoptotic protein and an important marker of organ damage, is regulated by post-translational modification.

E3 ubiquitin ligases in the acute leukemic signaling pathways.

Acute leukemia is a common hematologic tumor with highly genetic heterogeneity, and many factors are involved in the pathogenesis and drug-resistance mechanism. Emerging evidence proves that E3 ubiquitin ligases participate in the acute leukemic signaling pathways regulating substrates. This review summarized the E3 ligases which can affect the leukemic signal.

An unexpected role for BAG3 in regulating PARP1 ubiquitination in oxidative stress-related endothelial damage.

Oxidative stress-associated endothelial damage is the initiation factor of cardiovascular disease, and protein posttranslational modifications play critical roles in this process. Bcl-2-associated athanogene 3 (BAG3) is a molecular chaperone regulator of the BAG family, which interacts with various proteins and influences cell survival by activating multiple pathways. BAG3 undergoes posttranslational modifications; however, research evaluating BAG3 acetylation and its regulatory mechanism is lacking.

DNA Polymerase Gamma Recovers Mitochondrial Function and Inhibits Vascular Calcification by Interacted with p53.

DNA polymerase gamma (PolG) is the major polymerase of mitochondrial DNA (mtDNA) and essential for stabilizing mitochondrial function. Vascular calcification (VC) is common senescence related degenerative pathology phenomenon in the end-stage of multiple chronic diseases. Mitochondrial dysfunction was often observed in calcified vessels, but the function and mechanism of PolG in the calcification process was still unknown.

Deacetylation-dependent regulation of PARP1 by SIRT2 dictates ubiquitination of PARP1 in oxidative stress-induced vascular injury.

Poly(ADP-ribose) polymerase 1 (PARP1) has a major regulatory role in cardiovascular disease. However, inhibiting PARP1 activity does not significantly improve clinical outcomes of cardiovascular disease, which suggests that the regulatory mechanism of PARP1 in cardiovascular disease is unclear. Here, we focused on deacetylation regulatory mechanisms of PARP1 and crosstalk of PARP1 post-translational modifications.

Comprehensive Bioinformatics Analysis Identifies as a Key Gene in the Pathogenesis of Hypertensive Nephropathy.

Hypertensive nephropathy (HN), mainly caused by chronic hypertension, is one of the major causes of end-stage renal disease. However, the pathogenesis of HN remains unclarified, and there is an urgent need for improved treatments. Gene expression profiles for HN and normal tissue were obtained from the Gene Expression Omnibus database.

The role of SIRT2 in vascular-related and heart-related diseases: A review.

At present, cardiovascular disease is one of the important factors of human death, and there are many kinds of proteins involved. Sirtuins family proteins are involved in various physiological and pathological activities of the human body. Among them, there are more and more studies on the relationship between sirtuin2 (SIRT2) protein and cardiovascular diseases.

The deacetylation-phosphorylation regulation of SIRT2-SMC1A axis as a mechanism of antimitotic catastrophe in early tumorigenesis.

Improper distribution of chromosomes during mitosis can contribute to malignant transformation. Higher eukaryotes have evolved a mitotic catastrophe mechanism for eliminating mitosis-incompetent cells; however, the signaling cascade and its epigenetic regulation are poorly understood. Our analyses of human cancerous tissue revealed that the NAD-dependent deacetylase SIRT2 is up-regulated in early-stage carcinomas of various organs.

E3 Ubiquitin ligase NEDD4 family‑regulatory network in cardiovascular disease.

Protein ubiquitination represents a critical modification occurring after translation. E3 ligase catalyzes the covalent binding of ubiquitin to the protein substrate, which could be degraded. Ubiquitination as an important protein post-translational modification is closely related to cardiovascular disease.

The Role of BRG1 in Antioxidant and Redox Signaling.

Redox homeostasis is regulated by critical molecules that modulate antioxidant and redox signaling (ARS) within the cell. Imbalances among these molecules can lead to oxidative stress and damage to cell functions, causing a variety of diseases. Brahma-related gene 1 (BRG1), also known as SMARCA4, is the central ATPase catalytic subunit of the switch/sucrose nonfermentable (SWI/SNF) chromatin remodeling complex, which plays a core role in DNA replication, repair, recombination, and transcriptional regulation.

The Role of Mitochondria in Vascular Calcification.

Vascular calcification (VC) was defined as the ectopic deposition of calcium-phosphorus complexes on the blood vessel walls. It was a process involving multiple factors and mechanisms, covering the phenotype transition of vascular smooth muscle cells (VSMCs) and release of microvesicles. It was a common end-stage alteration of chronic diseases such as cardiovascular disease and chronic kidney disease.

Structure and Function of HECT E3 Ubiquitin Ligases and their Role in Oxidative Stress.

Ubiquitination is a modification after protein transcription that plays a vital role in maintaining the homeostasis of the cellular environment. The Homologous to E6AP C-terminus (HECT) family E3 ubiquitin ligases are a kind of E3 ubiquitin ligases with a C-terminal HECT domain that mediates the binding of ubiquitin to substrate proteins and a variable-length N-terminal extension. HECT-ubiquitinated ligases can be divided into three categories: NEDD4 superfamily, HERC superfamily, and other HECT superfamilies.

Role of WW domain E3 ubiquitin protein ligase 2 in modulating ubiquitination and Degradation of Septin4 in oxidative stress endothelial injury.

Oxidative stress-associated endothelial injury is the initial event and major cause of multiple cardiovascular diseases such as atherosclerosis and hypertensive angiopathy. A protein homeostasis imbalance is a critical cause of endothelial injury, and homologous to E6AP C-terminus (HECT)-type E3 ubiquitin ligases are the core factors controlling protein homeostasis. Although HECT-type E3 ubiquitin ligases are involved in the regulation of cardiac development and diseases, their roles in endothelial injury remain largely unknown.

Cul4a as a New Interaction Protein of PARP1 Inhibits Oxidative Stress-Induced H9c2 Cell Apoptosis.

Oxidative stress plays a major part in myocardial reperfusion injury. Cul4a is the core protein of CRLs E3 ubiquitin ligase complex; while it is known that Cul4a is responsible for various cancers, its role in cardiac function remains unclear. Hence, we have shown the protective function of Cul4a and its protection mechanism in oxidative stress-induced H9c2 cardiomyocyte apoptosis.