Cocaine exposure impairs multilineage hematopoiesis of human hematopoietic progenitor cells mediated by the sigma-1 receptor [corrected].
Prenatal exposure to cocaine is a significant source of fetal and neonatal developmental defects. While cocaine associated neurological and cardiac pathologies are well-documented, it is apparent that cocaine use has far more diverse physiological effects. It is known that in some cell types, the sigma-1 receptor mediates many of cocaine's cellular effects. Here we present a novel and concise investigation into the mechanism that underlies cocaine associated hematopoietic pathology. Indeed, this is the first examination of the effects of cocaine on hematopoiesis. We show that cocaine impairs multilineage hematopoiesis from human progenitors from multiple donors and tissue types. We go on to present the first demonstration of the expression of the sigma-1 receptor in human CD34 + human hematopoietic stem/progenitor cells. Furthermore, we demonstrate that these cocaine-induced hematopoietic defects can be reversed through sigma-1 receptor blockade.
1] Department of Microbiology, Immunology, &Molecular Genetics, UCLA [2] UCLA AIDS Institute, David Geffen School of Medicine, UCLA.
Christopher C
CC
Nixon
1] Department of Integrative Biology &Physiology, UCLA [2] UCLA AIDS Institute, David Geffen School of Medicine, UCLA.
Brandon H
BH
Schwartz
1] Department of Microbiology, Immunology, &Molecular Genetics, UCLA [2] UCLA AIDS Institute, David Geffen School of Medicine, UCLA.
Dhaval
D
Dixit
1] Department of Microbiology, Immunology, &Molecular Genetics, UCLA [2] Department of Hematology/Oncology, Division of Medicine, David Geffen School of Medicine, UCLA [3] UCLA AIDS Institute, David Geffen School of Medicine, UCLA.
Jerome A
JA
Zack
1] Department of Hematology/Oncology, Division of Medicine, David Geffen School of Medicine, UCLA [2] UCLA AIDS Institute, David Geffen School of Medicine, UCLA.
Dimitrios N
DN
Vatakis
D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D019070:Cell Lineage / Q000187:drug effects*; D002469:Cell Separation; D003042:Cocaine / Q000494:pharmacology*; D005312:Fetal Blood / Q000187:drug effects / Q000378:metabolism; D006410:Hematopoiesis / Q000187:drug effects*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D017480:Receptors, sigma / Q000378:metabolism*; D000097605:Sigma-1 Receptor
D018952:Antigens, CD34; D003042:Cocaine; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor