MicroRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease.
Summary of "MicroRNA miR-144 modulates oxidative stress tolerance and associates with anemia severity in sickle cell disease."
Although individuals with homozygous sickle cell disease (HbSS) share the same genetic mutation, the severity and manifestations of this disease are extremely heterogeneous. We have previously shown that the microRNA expression in HbAA and HbSS erythrocytes exhibit dramatic differences. In this study, we identify a subset of HbSS patients with higher erythrocytic miR-144 expression and more severe anemia. HbSS erythrocytes are known to have reduced tolerance for oxidative stress, yet the basis for this phenotype remains unknown. This study reveals that miR-144 directly regulates NRF2, a central regulator of cellular response to oxidative stress, and modulates the oxidative stress response in K562 cell line and primary erythroid progenitor cells. We further demonstrate that increased miR-144 is associated with reduced NRF2 levels in HbSS reticulocytes and with decreased glutathione regeneration and attenuated antioxidant capacity in HbSS erythrocytes, thereby providing a possible mechanism for the reduced oxidative stress tolerance and increased anemia severity seen in HbSS patients. Taken together, our findings suggest that erythroid microRNAs can serve as genetic modifiers of HbS-related anemia and can provide novel insights into the clinical heterogeneity and pathobiology of sickle cell disease.
Affiliation
The Institute for Genome Sciences and Policy, Duke University School of Medicine, Durham, NC, United States;
Journal Details
This article was published in the following journal.
Name: Blood
ISSN: 1528-0020
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20709907
- DOI: http://dx.doi.org/10.1182/blood-2009-04-214817
Medical and Biotech [MESH] Definitions
Oxidative Stress
A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi).
Fanconi Anemia Complementation Group Proteins
A diverse group of proteins whose genetic MUTATIONS have been associated with the chromosomal instability syndrome FANCONI ANEMIA. Many of these proteins play important roles in protecting CELLS against OXIDATIVE STRESS.
Protein Carbonylation
The appearance of carbonyl groups (such as aldehyde or ketone groups) in PROTEINS as the result of several oxidative modification reactions. It is a standard marker for OXIDATIVE STRESS. Carbonylated proteins tend to be more hydrophobic and resistant to proteolysis.
Tert-butylhydroperoxide
A direct-acting oxidative stress-inducing agent used to examine the effects of oxidant stress on Ca(2+)-dependent signal transduction in vascular endothelial cells. It is also used as a catalyst in polymerization reactions and to introduce peroxy groups into organic molecules.
Activating Transcription Factor 3
An activating transcription factor that plays a key role in cellular responses to GENOTOXIC STRESS and OXIDATIVE STRESS.
PubMed Articles
Despite many prior studies on microbial response to oxidative stress, our understanding of microbial tolerance against oxidative stress is currently limited to aerobic conditions, and few engineering...
The heterocystous nitrogen-fixing cyanobacterium, Anabaena sp. strain PCC7120 displayed two superoxide dismutase (SOD) activities, namely FeSOD and MnSOD. Prolonged exposure of Anabaena PCC7120 cells...
OsSYP71 is an oxidative stress and rice blast response gene that encodes a Qc-SNARE protein in rice. Qc-SNARE proteins belong to the superfamily of SNAREs (soluble N-ethylmaleimide-sensitive factor at...
Plasma membrane Ca(2+) transporters mediate virus-induced acquired resistance to oxidative stress.
This paper reports the phenomenon of acquired cross-tolerance to oxidative stress in plants and investigates the role and specific identity of transport systems mediating increased oxidative (UV-C) st...
The effect of carnitine on Arabidopsis development and recovery in salt stress conditions.
Carnitine exists in all living organisms where it plays diverse roles. In animals and yeast, it is implicated in lipid metabolism and is also associated with oxidative stress tolerance. In bacteria, i...
Clinical Trials
The main purpose of this longitudinal study is to point out the effect of VitabranE on the ESA resistance and on the anemia observed in HD patients undergoing EPO maintenance therapy. As...
Study of the Ability of Clarithromycin to Induce Oxidative Stress
The purpose of the study is to examine whether Klacid® (Clarithromycin) will induce oxidative stress (stress from oxygen) in healthy subjects. This is done by measuring the content of a p...
1. Treatment of Hypercholesterolemic patients with niacin will cause a significant decrease in oxidative stress and a decrease in the atherogenecity in blood samples of the patie...
The Effects of Acetylcysteine on Alleviating Damage of Oxidative Stress in Hemodialysis Patients
The aim of this study is to explore and identify the effects of acetylcysteine, a common mucolytic with anti-oxidant property, on alleviating the damage caused by increased oxidative stres...
The Comparison of Oxidative Stress Between Inhalation Anesthetics
Oxidative stress is an unavoidable event during cardiac surgery. Isoprostanes have been demonstrated to be a reliable biomarker for the evaluation of oxidative stress in vivo.The aims of t...
