Regulation of calcium homeostasis in endoplasmic reticulum–mitochondria crosstalk: implications for skeletal muscle atrophy

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 9, 2025

This review comprehensively explores the critical role of calcium as an essential small-molecule biomessenger in skeletal muscle function. Calcium is vital for both regulating excitation–contraction coupling and development, maintenance, regeneration cells. The orchestrated release from endoplasmic reticulum (ER) mediated by receptors such ryanodine receptor (RYR) inositol 1,4,5-trisphosphate (IP3R), which crucial contraction. sarcoendoplasmic ATPase (SERCA) pump plays a key recapturing calcium, enabling to return relaxed state. A pivotal aspect homeostasis involves dynamic interaction between mitochondria ER. includes local signaling facilitated RYRs "quasi-synaptic" mechanism formed IP3R-Grp75-VDAC/MCU axis, allowing rapid uptake with minimal interference at cytoplasmic level. Disruption transport can lead mitochondrial overload, triggering opening permeability transition pore subsequent reactive oxygen species cytochrome C, ultimately resulting damage atrophy. complex relationship ER how these organelles regulate levels muscle, aiming provide valuable perspectives future research on pathogenesis diseases development prevention strategies.

Language: Английский

---

Identification of Potential Diagnostic Biomarkers of Carotid Atherosclerosis in Obese Populations

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 1969 - 1991

Published: Feb. 1, 2025

Objective: This study aimed to investigate the potential mechanisms and biomarkers between Obesity (OB) carotid atherosclerosis (CAS). Methods: The GSE12828, GSE125771, GSE43292, GSE100927 datasets were combined normalized obtain CAS-related differentially expressed genes (DEGs), OB-related DEGs obtained from GSE151839 dataset GeneCards database. Unsupervised cluster analysis was conducted on CAS samples based of OB. Subsequently, immune infiltration gene set enrichment (GESA) performed. 61 machine learning models developed screen for Hub genes. Single-gene GESA focused calcium signaling pathway-related (CaRGs). Finally, high-fat diet-fed C57BL/6J ApoE −/− mice used in vivo validation. Results: MMP9, PLA2G7, SPP1 as regulators microenvironment OB patients with CAS, stratified into subtypes differences metabolic pathways classification. Enrichment indicated abnormalities inflammatory responses, signaling, lipid response obese patients. RF+GBM model identified CD52, CLEC5A, 15 CaRGs up-regulated, 12 down-regulated PLCB2, PRKCB, PLCG2 key pathway associated cell infiltration. In experiments showed that SPP1, FYB, PLCB2 mRNA levels up-regulated adipose, aortic tissues serum AS mice, CLEC5A aorta serum, PRKCB adipose serum. Conclusion: FYB may serve diagnostic populations. are CAS. These findings offer new insights clinical management therapeutic strategies individuals. Keywords: atherosclerosis, obesity, bioinformatics, unsupervised clustering analysis, model,

Language: Английский

---

Therapeutic Potential of Gasdermin D‐Mediated Myocardial Pyroptosis in Ischaemic Heart Disease: Expanding the Paradigm From Bench to Clinical Insights

Journal of Cellular and Molecular Medicine, Journal Year: 2025, Volume and Issue: 29(3)

Published: Feb. 1, 2025

ABSTRACT Ischaemic heart disease (IHD) remains a leading cause of global morbidity and mortality. One significant contributor to the pathology IHD is excessive release inflammatory mediators during progression. Pyroptosis form programmed cell death (PCD) triggered by activation inflammasomes caspase 1. The 1 proteolytically cleaves gasdermin D (GSDMD) activated amino acid terminus (GSDMD‐NT), disruption plasma membrane. This cascade events considered canonical pathway pyroptosis. also caused oxidative stress, thereby triggering noncanonical pyroptosis via caspases 4/5/11. Previous studies have provided compelling evidence close relationship between aetiology (e.g., acute myocardial infarction, ischaemia reperfusion injury chronic infarction), as well association with unfavourable clinical outcomes. Several interventions aimed at targeting demonstrated promising therapeutic benefits against IHD‐related pathologies. review provides mechanistic insights into roles in from vitro, vivo perspectives. In‐depth understanding this area could pave way for future development novel strategies IHD.

Language: Английский

---

Organellar crosstalk as a potential therapeutic target for rare neurodegenerative diseases

Rare Disease and Orphan Drugs Journal, Journal Year: 2025, Volume and Issue: 4(1)

Published: Feb. 28, 2025

Organellar crosstalk has gained significant interest due to its essential role in maintaining cellular homeostasis and normal function. Conversely, disruptions organelles their interactions are increasingly recognized as key contributors the pathogenesis of numerous diseases. Rare neurodegenerative diseases, such Gaucher disease (GD) X-linked adrenoleukodystrophy (ALD), caused by inherited mutations that disrupt critical metabolic pathways. Genetic variants encoding proteins involved these pathways result excessive accumulation corresponding substrates, which subsequently trigger organellar dysfunction, often involving mitochondria, lysosomes, endoplasmic reticulum (ER), or peroxisomes. To date, specific mechanisms underlying roles pathophysiology respective diseases not fully elucidated, an area continues be actively studied. Understanding could reveal novel targets for future therapeutic development. Furthermore, severity rare lack effective treatments forpatients underscore urgency thorough investigations into crosstalk. This review provides overview between ER, peroxisomes lysosomal GD, peroxisomal disorders, including ALD. Additionally, we explore potential strategies targeting interconnected

Language: Английский

---

Structure and Roles of Phospholipase C (PLC), Phosphatidylinositol 4,5-bisphosphate (PIP2), and Inositol 1,4,5-trisphosphate (IP3) in Metabolism and Disease: A Systematic Review

Innovations in Digital Health Diagnostics and Biomarkers, Journal Year: 2025, Volume and Issue: 5(2025), P. 1 - 13

Published: March 1, 2025

Abstract Phospholipase C (PLC) enzymes are vital for various body functions as they facilitate key signaling pathways that regulate numerous physiological processes. PLC in eukaryotic cells converts phosphatidylinositol 4,5-bisphosphate (PIP2) into inositol 1,4,5-triphosphate (IP3), and diacylglycerol, a pivotal pathway modulating intracellular calcium levels. The systematic review investigates the structural characteristics metabolic of PLC, PIP2, IP3 within human systems, examining isoform potential therapeutic applications. Specifically, different subfamilies isozymes across tissues can alter effect through distinct PIP2 binding affinities, enzyme expressions, activation modes, activity rates. an inner membrane component, participates multiple pathways—PLC, PI3K/AKT/mTOR, 5 phosphate—modulating diverse cellular functions. secondary messenger predominantly regulates Ca2+ levels via receptor-associated ion channels. Alterations this pathway, from mutations to receptor variations antagonist presence, impact with clinical implications. Therapeutic exists modulate specific PLC-PIP2-IP3 though certain targets challenging drug development due their critical roles complex networks. Further research is necessary comprehensively grasp implications targeting components.

Language: Английский

---

Preventive and Therapeutic Effects of Sericin-Derived Oligopeptides (SDOs) from Yellow Silk Cocoons on Blood Pressure Lowering in L-NAME-Induced Hypertensive Rats

Foods, Journal Year: 2025, Volume and Issue: 14(7), P. 1256 - 1256

Published: April 3, 2025

Our previous research has shown that SDOs derived from yellow silk cocoons have hypotensive effects on rats in chronic toxicity testing. This study investigated the potential preventative and therapeutic benefits of hypertensive induced by L-NAME. The experiment involved nine rat groups: (1) normal control, (2) + 200 mg kg-1 BW SDOs, (3) (HT) (4) HT 50 (5) 100 (6) (7) enalapril (Ena), (8) soy protein isolate (SPI), (9) bovine serum albumin (BSA). In approach, received 40 L-NAME with studied substances during four-week investigation. given at doses demonstrated a significant decrease systolic blood pressure (SBP) without affecting heart rate (HR). studies, increased SBP experimental groups over first four weeks, resulting mean values above 150 mmHg. Administering SPI significantly reduced SBP. However, exhibited closer to group. functional vascular tests, dose had highest relaxation lowest contraction percentages, like control groups. found may inhibit manage hypertension both healthy safeguarding endothelial cells.

Language: Английский

---