scholarly journals The Impact of Oxidative and Carbonyl Stress on Cell Function: Functional Consequences for Macrophages

2012 ◽  
pp. 88-98
Keyword(s):  
Cell Function ◽  
Carbonyl Stress ◽  
Functional Consequences ◽  
The Impact

scholarly journals Hypoxia and Hypoxia-Inducible Factor Signaling in Muscular Dystrophies: Cause and Consequences

2021 ◽  
Vol 22 (13) ◽  
pp. 7220
Author(s):  
Thuy-Hang Nguyen ◽  
Stephanie Conotte ◽  
Alexandra Belayew ◽  
Anne-Emilie Declèves ◽  
Alexandre Legrand ◽  
...  
Keyword(s):  
Cell Function ◽  
Current Knowledge ◽  
Genetic Defect ◽  
Hypoxia Inducible Factor ◽  
Muscular Dystrophies ◽  
Compensatory Mechanisms ◽  
Hypoxia Response ◽  
Muscle Disorders ◽  
Almost All ◽  
The Impact

Muscular dystrophies (MDs) are a group of inherited degenerative muscle disorders characterized by a progressive skeletal muscle wasting. Respiratory impairments and subsequent hypoxemia are encountered in a significant subgroup of patients in almost all MD forms. In response to hypoxic stress, compensatory mechanisms are activated especially through Hypoxia-Inducible Factor 1 α (HIF-1α). In healthy muscle, hypoxia and HIF-1α activation are known to affect oxidative stress balance and metabolism. Recent evidence has also highlighted HIF-1α as a regulator of myogenesis and satellite cell function. However, the impact of HIF-1α pathway modifications in MDs remains to be investigated. Multifactorial pathological mechanisms could lead to HIF-1α activation in patient skeletal muscles. In addition to the genetic defect per se, respiratory failure or blood vessel alterations could modify hypoxia response pathways. Here, we will discuss the current knowledge about the hypoxia response pathway alterations in MDs and address whether such changes could influence MD pathophysiology.

scholarly journals Age-Related Mitochondrial DNA Depletion and the Impact on Pancreatic Beta Cell Function

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e115433 ◽  
Author(s):  
Donna L. Nile ◽  
Audrey E. Brown ◽  
Meutia A. Kumaheri ◽  
Helen R. Blair ◽  
Alison Heggie ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Beta Cell ◽  
Beta Cell Function ◽  
Cell Function ◽  
Pancreatic Beta Cell ◽  
Age Related ◽  
Mitochondrial Dna Depletion ◽  
Pancreatic Beta Cell Function ◽  
The Impact

scholarly journals PKCδ Mediates Mineralocorticoid Receptor Activation by Angiotensin II to Modulate Smooth Muscle Cell Function

Endocrinology ◽  
2019 ◽  
Vol 160 (9) ◽  
pp. 2101-2114 ◽  
Author(s):  
Qing Lu ◽  
Ana P Davel ◽  
Adam P McGraw ◽  
Sitara P Rao ◽  
Brenna G Newfell ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Mineralocorticoid Receptor ◽  
Target Gene ◽  
Cell Function ◽  
Receptor Activation ◽  
Serine Phosphorylation ◽  
Dependent Manner ◽  
Responsive Element ◽  
The Impact

Abstract Angiotensin II (AngII) and the mineralocorticoid receptor (MR) ligand aldosterone both contribute to cardiovascular disorders, including hypertension and adverse vascular remodeling. We previously demonstrated that AngII activates MR-mediated gene transcription in human vascular smooth muscle cells (SMCs), yet the mechanism and the impact on SMC function are unknown. Using an MR-responsive element-driven transcriptional reporter assay, we confirm that AngII induces MR transcriptional activity in vascular SMCs and endothelial cells, but not in Cos1 or human embryonic kidney-293 cells. AngII activation of MR was blocked by the MR antagonist spironolactone or eplerenone and the protein kinase C-δ (PKCδ) inhibitor rottlerin, implicating both in the mechanism. Similarly, small interfering RNA knockdown of PKCδ in SMCs prevented AngII-mediated MR activation, whereas knocking down of MR blocked both aldosterone- and AngII-induced MR function. Coimmunoprecipitation studies reveal that endogenous MR and PKCδ form a complex in SMCs that is enhanced by AngII treatment in association with increased serine phosphorylation of the MR N terminus. AngII increased mRNA expression of the SMC-MR target gene, FKBP51, via an MR-responsive element in intron 5 of the FKBP51 gene. The impact of AngII on FKBP51 reporter activity and gene expression in SMCs was inhibited by spironolactone and rottlerin. Finally, the AngII-induced increase in SMC number was also blocked by the MR antagonist spironolactone and the PKCδ inhibitor rottlerin. These data demonstrate that AngII activates MR transcriptional regulatory activity, target gene regulation, and SMC proliferation in a PKCδ-dependent manner. This new mechanism may contribute to synergy between MR and AngII in driving SMC dysfunction and to the cardiovascular benefits of MR and AngII receptor blockade in humans.

scholarly journals Effects of Cryopreservation Duration on the Outcome of Single-Unit Cord Blood Transplantation

2018 ◽  
Vol 27 (3) ◽  
pp. 515-519 ◽  
Author(s):  
Tang-Her Jaing ◽  
Shih-Hsiang Chen ◽  
Yu-Chuan Wen ◽  
Tsung-Yen Chang ◽  
Ya-Chun Yang ◽  
...  
Keyword(s):  
Cord Blood ◽  
Clinical Outcomes ◽  
Progenitor Cell ◽  
Cell Function ◽  
Cord Blood Transplantation ◽  
Blood Transplantation ◽  
The Impact ◽  
Transplantation Outcomes ◽  
Neutrophil Engraftment

Cryopreservation is widely used in umbilical cord blood (UCB) banking, yet its impact on progenitor cell function remains largely unaddressed. It is unknown whether long-term cryopreservation affects UCB transplantation outcomes. Herein, we evaluated the impact of UCB age on clinical outcomes and investigated the effect of cryopreservation duration of UCB on hematopoietic potency in 91 patients receiving single cord blood transplantations. UCB cryopreservation duration was 0.7 to 13.4 y. The most common indication of transplant was thalassemia (48%). There was no significant association between cryopreservation duration and neutrophil engraftment probability ( P = 0.475). Cryopreservation duration did not affect the post-thaw viability and subsequent neutrophil engraftment rate. Therefore, UCB units can undergo cryopreservation for at least 8 y with no impact on clinical outcomes.

Abstract 353: Mechanical (or “Gravitational”) Unloading Reduces Inflammatory and Cell Adhesion Molecule Gene Expression in Human Endothelial Cells

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
S Marlene Grenon ◽  
Jesus Aguado-Zuniga ◽  
Michael Conte ◽  
Millie Hughes-Fulford
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Adhesion Molecule ◽  
Cell Function ◽  
Quantitative Polymerase Chain Reaction ◽  
Cellular Interactions ◽  
Gravitational Unloading ◽  
Experimental Conditions ◽  
Adhesion Molecule Gene ◽  
The Impact

Objectives: Mechanical forces including gravity affect mechanotransduction and subsequent cell function. The goal of this study was to investigate the impact of mechanical unloading (MU) and loading (ML) of endothelial cells (ECs) with microgravity and hypergravity respectively, with the hypothesis that MU alters expression of inflammatory and adhesion molecule gene expression and these changes are reversed by ML. Methods: Human umbilical vascular endothelial cells (HUVECs) grown to confluency were studied. A desktop random positioning machine and a gravitational cell-loading apparatus provided MU and ML conditions, respectively. The experimental conditions included: 1) controls exposed to 1-gravity environment for 24 h (CL), 2) MU for 24 hours, 3) MU for 24 hours with three 30-minutes periods of ML of 12-gravity (MU/ML). Gene expression was studied with reverse transcription followed by real-time quantitative polymerase chain reaction (qRTPCR). Results: MU led to a significant decrease in gene expression of the adhesion molecules ICAM-1, VCAM-1, E-Selectin, as well as TNF-α, IL-6 and VEGF. In contrast, NOS-3, Caveolin-1 and -2 were significantly increased with MU. The changes observed in gene expression with MU were reversed by gravitational mechanical loading (MU/ML). Conclusions: Gravitational MU decreases inflammatory and adhesion molecule gene expression and these changes are reversed by short periods of ML. This points towards the importance of gravitational loading in ECs function and cellular interactions.

scholarly journals Effect of Inflammation on Female Gonadotropin-Releasing Hormone (GnRH) Neurons: Mechanisms and Consequences

2020 ◽  
Vol 21 (2) ◽  
pp. 529 ◽  
Author(s):  
Klaudia Barabás ◽  
Edina Szabó-Meleg ◽  
István M. Ábrahám
Keyword(s):  
Suppressive Effect ◽  
Gonadotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Inflammatory Signals ◽  
Cholinergic Pathway ◽  
Gnrh Neurons ◽  
Functional Consequences ◽  
Anti Inflammatory ◽  
The Impact

Inflammation has a well-known suppressive effect on fertility. The function of gonadotropin-releasing hormone (GnRH) neurons, the central regulator of fertility is substantially altered during inflammation in females. In our review we discuss the latest results on how the function of GnRH neurons is modified by inflammation in females. We first address the various effects of inflammation on GnRH neurons and their functional consequences. Second, we survey the possible mechanisms underlying the inflammation-induced actions on GnRH neurons. The role of several factors will be discerned in transmitting inflammatory signals to the GnRH neurons: cytokines, kisspeptin, RFamide-related peptides, estradiol and the anti-inflammatory cholinergic pathway. Since aging and obesity are both characterized by reproductive decline our review also focuses on the mechanisms and pathophysiological consequences of the impact of inflammation on GnRH neurons in aging and obesity.

scholarly journals CD38 deletion of human primary NK cells eliminates daratumumab-induced fratricide and boosts their effector activity

Blood ◽  
2020 ◽  
Vol 136 (21) ◽  
pp. 2416-2427 ◽  
Author(s):  
Meisam Naeimi Kararoudi ◽  
Yuya Nagai ◽  
Ezgi Elmas ◽  
Marcelo de Souza Fernandes Pereira ◽  
Syed Abbas Ali ◽  
...  
Keyword(s):  
Nk Cells ◽  
Cell Function ◽  
Nk Cell ◽  
Ex Vivo ◽  
Human Monoclonal Antibody ◽  
Metabolic Reprogramming ◽  
Target Cells ◽  
Plasma Cell Neoplasm ◽  
Cd38 Expression ◽  
The Impact

Abstract Multiple myeloma (MM) is a plasma cell neoplasm that commonly expresses CD38. Daratumumab (DARA), a human monoclonal antibody targeting CD38, has significantly improved the outcome of patients with relapsed or refractory MM, but the response is transient in most cases. Putative mechanisms of suboptimal efficacy of DARA include downregulation of CD38 expression and overexpression of complement inhibitory proteins on MM target cells as well as DARA-induced depletion of CD38high natural killer (NK) cells resulting in crippled antibody-dependent cellular cytotoxicity (ADCC). Here, we tested whether maintaining NK cell function during DARA therapy could maximize DARA-mediated ADCC against MM cells and deepen the response. We used the CRISPR/Cas9 system to delete CD38 (CD38KO) in ex vivo expanded peripheral blood NK cells. These CD38KO NK cells were completely resistant to DARA-induced fratricide, showed superior persistence in immune-deficient mice pretreated with DARA, and enhanced ADCC activity against CD38-expressing MM cell lines and primary MM cells. In addition, transcriptomic and cellular metabolic analysis demonstrated that CD38KO NK cells have unique metabolic reprogramming with higher mitochondrial respiratory capacity. Finally, we evaluated the impact of exposure to all-trans retinoic acid (ATRA) on wild-type NK and CD38KO NK cell function and highlighted potential benefits and drawbacks of combining ATRA with DARA in patients with MM. Taken together, these findings provide proof of concept that adoptive immunotherapy using ex vivo expanded CD38KO NK cells has the potential to boost DARA activity in MM.

scholarly journals Potential Impact of B Cells on T Cell Function in Multiple Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Sara Ireland ◽  
Nancy Monson
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cell Function ◽  
The Central Nervous System ◽  
Potential Impact ◽  
Anti Cd20 ◽  
The Impact ◽  
Ms Pathogenesis

Multiple sclerosis is a chronic debilitating autoimmune disease of the central nervous system. The contribution of B cells in the pathoetiology of MS has recently been highlighted by the emergence of rituximab, an anti-CD20 monoclonal antibody that specifically depletes B cells, as a potent immunomodulatory therapy for the treatment of MS. However, a clearer understanding of the impact B cells have on the neuro-inflammatory component of MS pathogenesis is needed in order to develop novel therapeutics whose affects on B cells would be beneficial and not harmful. Since T cells are known mediators of the pathology of MS, the goal of this review is to summarize what is known about the interactions between B cells and T cells, and how current and emerging immunotherapies may impact B-T cell interactions in MS.

scholarly journals CNGA3 achromatopsia-associated mutation potentiates the phosphoinositide sensitivity of cone photoreceptor CNG channels by altering intersubunit interactions

2013 ◽  
Vol 305 (2) ◽  
pp. C147-C159 ◽  
Author(s):  
Gucan Dai ◽  
Michael D. Varnum
Keyword(s):  
Leucine Zipper ◽  
Sensory Transduction ◽  
Cone Photoreceptor ◽  
Electrophysiological Recordings ◽  
Retinal Photoreceptors ◽  
Functional Consequences ◽  
Interdomain Interaction ◽  
Channel Assembly ◽  
Intersubunit Interactions ◽  
The Impact

Cyclic nucleotide-gated (CNG) channels are critical for sensory transduction in retinal photoreceptors and olfactory receptor cells; their activity is modulated by phosphoinositides (PIPn) such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3). An achromatopsia-associated mutation in cone photoreceptor CNGA3, L633P, is located in a carboxyl (COOH)-terminal leucine zipper domain shown previously to be important for channel assembly and PIPn regulation. We determined the functional consequences of this mutation using electrophysiological recordings of patches excised from cells expressing wild-type and mutant CNG channel subunits. CNGA3-L633P subunits formed functional channels with or without CNGB3, producing an increase in apparent cGMP affinity. Surprisingly, L633P dramatically potentiated PIPn inhibition of apparent cGMP affinity for these channels. The impact of L633P on PIPn sensitivity depended on an intact amino (NH2) terminal PIPn regulation module. These observations led us to hypothesize that L633P enhances PIPn inhibition by altering the coupling between NH2- and COOH-terminal regions of CNGA3. A recombinant COOH-terminal fragment partially restored normal PIPn sensitivity to channels with COOH-terminal truncation, but L633P prevented this effect. Furthermore, coimmunoprecipitation of channel fragments, and thermodynamic linkage analysis, also provided evidence for NH2-COOH interactions. Finally, tandem dimers of CNGA3 subunits that specify the arrangement of subunits containing L633P and other mutations indicated that the putative interdomain interaction occurs between channel subunits (intersubunit) rather than exclusively within the same subunit (intrasubunit). Collectively, these studies support a model in which intersubunit interactions control the sensitivity of cone CNG channels to regulation by phosphoinositides. Aberrant channel regulation may contribute to disease progression in patients with the L633P mutation.

Sign in / Sign up

Export Citation Format

Share Document