Nixon Christopher C, Schwartz Brandon H, Dixit Dhaval, Zack Jerome A, Vatakis Dimitrios N
1] Department of Microbiology, Immunology, &Molecular Genetics, UCLA [2] UCLA AIDS Institute, David Geffen School of Medicine, UCLA.
1] Department of Integrative Biology &Physiology, UCLA [2] UCLA AIDS Institute, David Geffen School of Medicine, UCLA.
Sci Rep. 2015 Mar 2;5:8670. doi: 10.1038/srep08670.
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.
产前接触可卡因是胎儿和新生儿发育缺陷的一个重要来源。虽然可卡因相关的神经和心脏病理学已有充分记录，但显然可卡因的使用具有更多样化的生理效应。已知在某些细胞类型中，σ-1受体介导了可卡因的许多细胞效应。在此，我们对可卡因相关造血病理学的潜在机制进行了新颖而简洁的研究。事实上，这是首次对可卡因对造血作用的研究。我们表明，可卡因会损害来自多个供体和组织类型的人类祖细胞的多谱系造血。我们接着首次证明了σ-1受体在人类CD34 + 人类造血干细胞/祖细胞中的表达。此外，我们证明这些可卡因诱导的造血缺陷可通过σ-1受体阻断得以逆转。
