Mitochondria defects are involved in lead-acetate-induced adult hematopoietic stem cell decline.

Abstract:

:Occupational high-grade lead exposure has been reduced in recent decades as a result of increased regulation. However, environmental lead exposure remains widespread, and is associated with severe toxicity implicated in human diseases. We performed oral intragastric administration of various dose lead acetate to adult Sprague Dawley rats to define the role of lead exposure in hematopoietic stem cells (HSCs) function, and to clarify its underlying mechanism. Lead acetate-exposed rats exhibited developmental abnormalities in myeloid and lymphoid lineages, and a significant decline in immune functions. It also showed HSCs functional decline associated with senescent phenotype with low grade lead acetate exposure or apoptotic phenotype with relative higher grade dose exposure. Mechanistic exploration showed a significant increase in reactive oxygen species (ROS) in the lead acetate-exposed CD90(+)CD45(-) compartment, which correlated with functional defects in cellular mitochondria. Furthermore, in vivo treatment with the antioxidant vitamin C led to reversion of the CD90(+)CD45(-) compartment functional decline. These results indicate that lead acetate perturbs the hematopoietic balance of adult HSCs, associated with cellular mitochondria defects, increased intracellular ROS generation.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

Liu J,Jia DY,Cai SZ,Li CP,Zhang MS,Zhang YY,Yan CH,Wang YP

doi

10.1016/j.toxlet.2015.03.007

subject

Has Abstract

pub_date

2015-05-19 00:00:00

pages

37-44

issue

1

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(15)00110-1

journal_volume

235

pub_type

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