The G protein-coupled serotonin 5-hydroxytryptamine (5-HT)_2A receptor is primarily recognized for its role in brain neurotransmission, where it mediates a wide variety of functions, including certain aspects cognition. However, there significant expression this peripheral tissues, importance largely unknown. We have now discovered that activation 5-HT_2A receptors primary aortic smooth muscle cells provides previously unknown and extremely potent inhibition tumor...

Abstract The role of NF-κB in the expression inflammatory genes and its participation overall process chronic diseases acute tissue injury are well established. We others have demonstrated a critical involvement poly(ADP-ribose) polymerase (PARP)-1 during inflammation, part, through relationship with NF-κB. However, mechanism by which PARP-1 affects activation has been elusive. In this study, we show that inhibition gene knockout, knockdown, or pharmacologic blockade prevented p65 nuclear...

Introduction—heterogeneity in clinical outcomes and survival was observed patients with papillary thyroid cancer (PTC) distant metastases. Here, we investigated the effect of metastases sites on PTC patients. Methods—patients a diagnosis known were identified using Surveillance, Epidemiology, End Results database (1975–2016). Univariate multivariate Cox regression analyses performed to analyze cancer-specific (TCSS) overall (OS). Results—from 89,694 patients, 1819 (2%) developed metastasis...

Phagocytosis of apoptotic cells by macrophages, known as efferocytosis, is a critical process in the resolution inflammation. High mobility group box 1 (HMGB1) protein was first described nuclear nonhistone DNA-binding protein, but now to be secreted activated during inflammatory processes, where it participates diminishing efferocytosis. Although HMGB1 undergo modification when secreted, effect such modifications on inhibitory actions efferocytosis have not been reported. In present...

This study compares the suppression of Mitogen-activated protein kinase (MAPK) signalling and early resistance potential between a proteolysis-targeting chimera (PROTAC) inhibitors targeting BRAFV600E. We performed detailed in silico analysis transcriptomic landscape A375 melanoma cell line treated with PROTAC BRAFV600E from RNA sequencing data. The assessed gene dysregulation, MAPK Phosphoinositide-3-kinase (PI3K/AKT) pathway inhibition, survival. Key genes uniquely dysregulated by...

This study determines that vascular smooth muscle cell (VSMC) signaling through extracellular signal-regulated kinase (ERK) 1/2-mitogen-activated protein (MAP) kinase, alphavbeta(3)-integrin, and transforming growth factor (TGF)-beta1 dictates collagen type I network induction in mesenteric resistance arteries (MRA) from 1 diabetic (streptozotocin) or hypertensive (HT; ANG II) mice. Isolated MRA were subjected to a pressure-passive-diameter relationship. To delineate types mechanisms,...

Abstract The role of inducible NO synthase (iNOS) in allergic airway inflammation remains elusive. We tested the hypothesis that iNOS plays different roles during acute versus chronic inflammation. Acute and mouse models OVA-induced were used to conduct study. showed deletion was associated with a reduction eosinophilia, mucus hypersecretion, IL-5 IL-13 production upon protocol. Such protection completely abolished Interestingly, pulmonary fibrosis observed wild-type mice under protocol...

To cite this article: Datta R, Naura AS, Zerfaoui M, Errami Y, Oumouna Kim H, Ju J, Ronchi VP, Haas AL, Boulares AH. PARP-1 deficiency blocks IL-5 expression through calpain-dependent degradation of STAT-6 in a murine asthma model. Allergy 2011; 66: 853–861. Background: We recently showed that poly(ADP-ribose)polymerase-1 (PARP-1) may play role allergen (ovalbumin)-induced airway eosinophilia, potentially specific effect on production. also reported while replenishment promotes reversal...

The uptake and clearance of apoptotic cells by macrophages other phagocytic cells, a process called efferocytosis, is major component in the resolution inflammation. Increased concentrations extracellular histones are found during acute inflammatory states appear to contribute organ system dysfunction mortality. In these studies, we examined potential role modulating efferocytosis. We that phagocytosis neutrophils or thymocytes was significantly diminished presence H3 H4, but not histone H1....

The aim of this study was to take a combination animal and cell culture approaches examine the individual responses vascular cells varying inflammatory factors in order gain insights on mechanism(s) by which poly(ADP-ribose) polymerase (PARP) inhibition promotes plaque stability. Apolipoprotein (ApoE−/−) mice fed high-fat diet were used as model atherosclerosis. Primary endothelial cells, smooth muscle (SMCs), ex-vivo generated foam (FCs) our vitro studies. PARP significantly decreased...

We recently showed that poly(ADP-ribose) polymerase (PARP) is activated within atherosclerotic plaques in an animal model of atherosclerosis. Pharmacological inhibition PARP or reduced expression heterozygous animals interferes with atherogenesis and may promote factors plaque stability, possibly reflecting changes inflammatory cellular consistent stability. The current study addresses the hypothesis pharmacological promotes regression. Using a high-fat diet-induced atherosclerosis...

Summary Background Identifying therapeutic drugs that block the release or effects of T‐helper type 2 (Th2) cytokines after allergen exposure is an important goal for treatment allergic inflammatory diseases including asthma. We recently showed, using a murine model airway inflammation, poly(ADP‐ribose) polymerase (PARP) plays role in pathogenesis asthma‐related lung inflammation. PARP inhibition, by single injection novel inhibitor, thieno[2,3‐c]isoquinolin‐5‐one (TIQ‐A), before ovalbumin...

Inducible nitric oxide synthase (iNOS) inhibition was recently shown to exert no effect on allergen challenge in human asthma, raising serious concerns about the role of protein disease. The present study investigated iNOS ovalbumin-induced eosinophilia from perspective its relationship with poly(ADP-ribose) polymerase-1 (PARP-1) and oxidative DNA damage. A mouse model used conduct studies. iNOS-associated nitration tissue damage were partially responsible for allergen-induced eosinophilia....

The aims of this study were to investigate the role poly(ADP-ribose) polymerase (PARP)-1 in dyslipidemia-associated vascular dysfunction as well autonomic nervous system dysregulation. Apolipoprotein (ApoE)(-/-) mice fed a high-fat diet used model atherosclerosis. Vascular and functions measured conscious using telemetry. revealed that PARP-1 plays an important dysfunction. Inhibition enzyme by gene knockout partially restored baroreflex sensitivity ApoE(-/-) without affecting baseline...

Abstract Although the utilization of selective BRAF V600E inhibitors is associated with improved overall survival in patients metastatic melanoma, a growing challenge drug resistance has emerged. CDC7 been shown to be overexpressed and poor prognosis various cancers including melanoma. Thus, we aimed elucidate biological role promoting Vemurafenib anticipated benefits dual targeting melanoma cells. We performed exosomes-associated microRNA profiling functional assays determine using...

The β1,6 N-acetylglucosaminyltransferase (C2GnT) has been recently mapped to the cis/medial-Golgi compartment. To analyze Golgi-targeting determinants of C2GnT, we constructed various deletion mutants enzyme fused enhanced green fluorescent protein (EGFP) and localized these proteins by fluorescence microscopy in living cells. We found that N-terminal peptide encompassing amino acids 1 32 represents minimal signal sufficient localize EGFP same compartment as full-length C2GnT. This makes up...

Journal Article Effects of PARP-1 deficiency on airway inflammatory cell recruitment in response to LPS or TNF: differential effects CXCR2 ligands and Duffy antigen receptor for chemokines Get access Mourad Zerfaoui, Zerfaoui Department Pharmacology Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA Search other works by this author on: Oxford Academic Google Scholar Amarjit S Naura, Naura Youssef Errami, Errami Chetan P Hans, Hans...