Trpv1 and Trpa1 are not essential for Psickle-like activity in red cells of the SAD mouse model of sickle cell disease.

Autor: Vandorpe DH; Division of Nephrology, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States of America; Department of Medicine, Harvard Medical School, Boston, MA 02115, United States of America., Rivera A; Division of Nephrology, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States of America; Department of Medicine, Harvard Medical School, Boston, MA 02115, United States of America., Shmukler BE; Division of Nephrology, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States of America; Department of Medicine, Harvard Medical School, Boston, MA 02115, United States of America., Wohlgemuth JG; Quest Diagnostics, Inc., Seacaucus, NJ 07094, United States of America., Dlott JS; Quest Diagnostics, Inc., Seacaucus, NJ 07094, United States of America., Snyder LM; Quest Diagnostics, Inc., Seacaucus, NJ 07094, United States of America., Trudel M; Institut de Recherches Cliniques de Montreal, Universite de Montreal, Montreal, QC H2W 1R7, Canada., Brugnara C; Department of Laboratory Medicine, Boston Children's Hospital, Boston, MA 02115, United States of America; Department of Pathology, Harvard Medical School, Boston, MA 02115, United States of America., Alper SL; Division of Nephrology, Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, United States of America; Department of Medicine, Harvard Medical School, Boston, MA 02115, United States of America. Electronic address: salper@bidmc.harvard.edu.
Jazyk: angličtina
Zdroj: Blood cells, molecules & diseases [Blood Cells Mol Dis] 2021 Dec; Vol. 92, pp. 102619. Date of Electronic Publication: 2021 Oct 29.
DOI: 10.1016/j.bcmd.2021.102619
Abstrakt: The molecular identity of Psickle, the deoxygenation-activated cation conductance of the human sickle erythrocyte, remains unknown. We observed in human sickle red cells that inhibitors of TRPA1 and TRPV1 inhibited Psickle, whereas a TRPV1 agonist activated a Psickle-like cation current. These observations prompted us to test the roles of TRPV1 and TRPA1 in Psickle in red cells of the SAD mouse model of sickle cell disease. We generated SAD mice genetically deficient in either TRPV1 or TRPA1. SAD;Trpv1 -/- and SAD;Trpa1 -/- mice were indistinguishable in appearance, hematological indices, and osmotic fragility from SAD mice. We found that deoxygenation-activated cation currents remained robust in SAD;Trpa1 -/- and SAD;Trpv1 -/- mice. In addition, 45 Ca 2+ influx into SAD mouse red cells during prolonged deoxygenation was not reduced in red cells from SAD;Trpa1 -/- and SAD;Trpv1 -/- mice. We conclude that the nonspecific cation channels TRPA1 and TRPV1 are not required for deoxygenation to stimulate Psickle-like activity in red cells of the SAD mouse model of sickle cell disease. (159).
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
Externí odkaz: