PARP‐1 Inhibition Increases Oxidative Stress in Ets‐1‐Expressing MDA‐MB‐231 Breast Cancer Cells

Cancer Reports, Journal Year: 2025, Volume and Issue: 8(1)

Published: Jan. 1, 2025

The Ets-1 transcription factor plays a primordial role in regulating the expression of numerous genes implicated cancer progression. In previous study, we revealed that poly(ADP-ribose) polymerase-1 (PARP-1) inhibition by PJ-34 results level increase cells, which is related with cell death Ets-1-expressing cells. mechanism antitumor effect PARP-1 was investigated MDA-MB-231 breast We tested effects four PARP inhibitors (PARPi) (PJ-34, Veliparib, Olaparib, and Rucaparib). first demonstrated PARPi reduced cells growth through G2/M cycle arrest. Next, evaluated on oxidative DNA damage Ets-1-overexpressing Ets-1-non-expressing showed led only to accumulate it, triggers response as panel damage-related proteins. Importantly, increased reactive oxygen species (ROS), this accompanied upregulation p47phox expression, subunit NAPDH oxidase (NOX). These preliminary findings correlate PARPi-induced damage/oxidative stress

Language: Английский

---

Deciphering the dark side of histone ADP-ribosylation: what structural features of damaged nucleosome regulate the activities of PARP1 and PARP2

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 30, 2025

ABSTRACT Poly(ADP-ribose) polymerases are critical enzymes contributing to regulation of numerous cellular processes, including DNA repair. Within the PARP family, PARP1 and PARP2 primarily facilitate PARylation in nucleus, particularly responding genotoxic stress. The activity PARPs is influenced by nature damage multiple protein partners, with HPF1 being important one. Forming a joint active site (PARP2), contributes histone following chromatin remodelling during stress events. This study elucidates interrelation between presence location one-nucleotide gap within nucleosome core particle (NCP) activities automodification heteromodification histones. Utilizing combination classical biochemical methods fluorescence-based technique single-molecule mass photometry approach, we have shown that NCP architecture impacts efficiency pattern ADP-ribosylation binding histones-associated damaged more significantly for than PARP1. Analysis based on existing studies HPF1-dependent ADP-ribosylome structural dynamics allows suggest conformational flexibility tails modulated post-translational modifications crucial delineating distinct roles responses. GRAPHICAL

Language: Английский

---

Nicotinamide: A Multifaceted Molecule in Skin Health and Beyond

Medicina, Journal Year: 2025, Volume and Issue: 61(2), P. 254 - 254

Published: Feb. 1, 2025

Nicotinamide (NAM), the amide form of vitamin B3, is a precursor to essential cofactors nicotinamide adenine dinucleotide (NAD⁺) and NADPH. NAD⁺ integral numerous cellular processes, including metabolism regulation, ATP production, mitochondrial respiration, reactive oxygen species (ROS) management, DNA repair, senescence, aging. NAM supplementation has demonstrated efficacy in restoring energy, repairing damage, inhibiting inflammation by suppressing pro-inflammatory cytokines release. Due its natural presence variety foods excellent safety profile—even at high doses up 3 g/day—NAM extensively used chemoprevention non-melanoma skin cancers treatment dermatological conditions such as blistering diseases, atopic dermatitis, rosacea, acne vulgaris. Recently, anti-aging properties have elevated NAM’s prominence skincare formulations. Beyond repair energy replenishment, significantly impacts oxidative stress reduction, cell cycle apoptosis modulation. Despite these multifaceted benefits, comprehensive molecular mechanisms underlying actions remain not fully elucidated. This review consolidates recent research shed light on mechanisms, emphasizing critical role health therapeutic potential. By enhancing our understanding, this work underscores importance continued exploration into applications, aiming inform future clinical practices innovations.

Language: Английский

---

XRCC1 mediates PARP1- and PAR-dependent recruitment of PARP2 to DNA damage sites

Nucleic Acids Research, Journal Year: 2025, Volume and Issue: 53(4)

Published: Feb. 8, 2025

Abstract Poly-ADP-ribose polymerases 1 and 2 (PARP1 2) are critical sensors of DNA-strand breaks targets for cancer therapy. Upon DNA damage, PARP1 synthesize poly-ADP-ribose (PAR) chains on themselves other substrates, facilitating single-strand break repair by recruiting PAR-binding factors, including X-ray cross-complementing group (XRCC1) aprataxin polynucleotide kinase phosphatase-like factor (APLF). While diverse lesions activate PARP1, PARP2 is selectively activated 5′ phosphorylated nicks. They function independently compensate each other. Previous studies suggest that its PAR act upstream to recruit damage sites. Here, we report the scaffold protein XRCC1 mediates PARP1- PAR-dependent recruitment XRCC1-deficiency causes hyperactivation while attenuating micro-irradiation-induced foci. Mechanistically, BRCT1 domain binds PAR, BRCT2 interacts with catalytic enzymatic activity LIG3 BRCT via residues D575 Y576. This mode enrichment important certain proteins, such as APLF, but dispensable others, XRCC1–BRCT1 domain. These findings highlight distinct role in synthesis uncover unexpected hierarchical roles PARP2.

Language: Английский

---

Mitochondrial dysfunction in PBMC: a potential sensor for metabolic dysfunction-associated steatotic liver disease and therapeutic insight for NAD+-increasing strategies

Published: Feb. 26, 2025

The epidemic of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly growing worldwide. Thus, there an urgent need for novel, non-invasive, and reliable biomarkers to replace biopsy the diagnosis prognosis MASLD. Circulating peripheral blood mononuclear cells (PBMCs) are highly responsive various stimuli physiological changes. Beyond their immunomodulatory role, PBMC may act as sensors in several cardiometabolic disorders, including MASLD, with programs shifting accordingly. Recent evidence suggests a link between impaired mitochondrial bioenergetics Additionally, respiration intricately linked intracellular depletion oxidized form nicotinamide adenine dinucleotide (NAD+) cell types. Accumulating preclinical clinical data show that NAD+-increasing strategies protect against MASLD by restoring NAD+ pools improving performance. This review will focus on [i] relevance dysfunction, bioenergetics, marker [ii] potential benefits precursors MAFLD relationship improved immune cells.

Language: Английский

---

Targeting PCNA/PARP1 axis inhibits the malignant progression of hepatocellular carcinoma

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: April 17, 2025

Introduction Proliferating cell nuclear antigen (PCNA) is associated with the proliferation and recurrence of various cancers, its high expression poor prognosis in hepatocellular carcinoma (HCC) patients. However, mechanistic role PCNA HCC progression remains poorly understood. This study aimed to investigate how regulates DNA damage repair cycle HCC, a focus on interaction poly (ADP-ribose) polymerase 1 (PARP1) therapeutic implications. Methods was targeted genetically pharmacologically cells assess effects arrest. Protein-protein interactions between PARP1 were validated through co-immunoprecipitation functional assays. The sensitivity inhibitor Olaparib evaluated under inhibition. Synergistic AOH1160 (a inhibitor) tested vitro vivo using assays, quantification, analysis. Prognostic relevance analyzed TCGA datasets. Results Targeting suppressed induced arrest cells. Mechanistically, identified as downstream target directly interacted PCNA. Inhibiting or activity increased inhibitor, Olaparib. In addition, synergistically inhibited proliferation, Elevated levels correlated unfavorable prognosis, supporting biomarker. experiments also confirmed that repression PCNA/PARP1 axis significantly reduced tumor growth. Discussion elucidates relationship regulating malignant highlight pivotal progression. correlation elevated underscores potential Repression inhibits both vivo. Collectively, provides foundation for therapies targeting axis.

Language: Английский

---

FOXD3 promotes homologous recombination repair and genomic stability by facilitating MRE11-mediated DNA end resection

Acta Biochimica et Biophysica Sinica, Journal Year: 2025, Volume and Issue: unknown

Published: April 1, 2025

Language: Английский

---

The poly(ADP-ribosyl)ation system in the crustacean copepod Temora stylifera (Dana, 1853–1855) from a coastal area of the Mediterranean Sea: a new biomarker of the health status

Euro-Mediterranean Journal for Environmental Integration, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 28, 2024

Language: Английский

---