Kaiqi Sun1, Yang Xia. 1. Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas 77030, USA.
Abstract
PURPOSE OF REVIEW: Sickle cell disease (SCD) is a devastating genetic disorder caused by a single amino acid substitution in β-globin. Although the condition was first described more than a 100 years ago, treatment options remain scarce and unsatisfactory. This review summarizes recent findings that may provide novel insight into therapeutic approaches to SCD treatment. RECENT FINDINGS: Because of insufficient numbers of erythrocytes for oxygen delivery, SCD patients constantly face hypoxia. Adenosine is well known as a key signaling nucleoside that orchestrates a multifaceted physiological response to hypoxia. Recent studies have revealed that adenosine concentrations are significantly elevated in SCD and contribute to disease pathology by activating adenosine receptors on red blood cells. Apart from adenosine, hypoxia also causes hemoglobin release via hemolysis. Studies on free hemoglobin in circulation have uncovered another two important molecules: nitric oxide and heme oxygenase-1. SUMMARY: The core of SCD pathology is erythrocyte sickling under hypoxic conditions, leading to vaso-occlusion and hemolysis. Deeper and more comprehensive understanding of SCD as a disease of hypoxia will provide us new therapeutic targets for SCD treatment.
PURPOSE OF REVIEW: Sickle cell disease (SCD) is a devastating genetic disorder caused by a single amino acid substitution in β-globin. Although the condition was first described more than a 100 years ago, treatment options remain scarce and unsatisfactory. This review summarizes recent findings that may provide novel insight into therapeutic approaches to SCD treatment. RECENT FINDINGS: Because of insufficient numbers of erythrocytes for oxygen delivery, SCDpatients constantly face hypoxia. Adenosine is well known as a key signaling nucleoside that orchestrates a multifaceted physiological response to hypoxia. Recent studies have revealed that adenosine concentrations are significantly elevated in SCD and contribute to disease pathology by activating adenosine receptors on red blood cells. Apart from adenosine, hypoxia also causes hemoglobin release via hemolysis. Studies on free hemoglobin in circulation have uncovered another two important molecules: nitric oxide and heme oxygenase-1. SUMMARY: The core of SCD pathology is erythrocyte sickling under hypoxic conditions, leading to vaso-occlusion and hemolysis. Deeper and more comprehensive understanding of SCD as a disease of hypoxia will provide us new therapeutic targets for SCD treatment.
Authors: Kaiqi Sun; Yujin Zhang; Mikhail V Bogdanov; Hongyu Wu; Anren Song; Jessica Li; William Dowhan; Modupe Idowu; Harinder S Juneja; Jose G Molina; Michael R Blackburn; Rodney E Kellems; Yang Xia Journal: Blood Date: 2015-01-13 Impact factor: 22.113
Authors: Hong Liu; Morayo Adebiyi; Rong Rong Liu; Anren Song; Jeanne Manalo; Yuan Edward Wen; Alexander Q Wen; Tingting Weng; Junsuk Ko; Modupe Idowu; Rodney E Kellems; Holger K Eltzschig; Michael R Blackburn; Harinder S Juneja; Yang Xia Journal: Blood Adv Date: 2018-08-14
Authors: Hong Liu; Yujin Zhang; Hongyu Wu; Angelo D'Alessandro; Gennady G Yegutkin; Anren Song; Kaiqi Sun; Jessica Li; Ning-Yuan Cheng; Aji Huang; Yuan Edward Wen; Ting Ting Weng; Fayong Luo; Travis Nemkov; Hong Sun; Rodney E Kellems; Harry Karmouty-Quintana; Kirk C Hansen; Bihong Zhao; Andrew W Subudhi; Sonja Jameson-Van Houten; Colleen G Julian; Andrew T Lovering; Holger K Eltzschig; Michael R Blackburn; Robert C Roach; Yang Xia Journal: Circulation Date: 2016-08-02 Impact factor: 29.690
Authors: Jing Li; Si-Yeon Jeong; Bei Xiong; Alan Tseng; Andrew B Mahon; Steven Isaacman; Victor R Gordeuk; Jaehyung Cho Journal: Haematologica Date: 2019-10-31 Impact factor: 9.941