Abstract
AimsSome environmental insults, such as fine particulate matter (PM) exposure, significantly impair the function of stem cells. However, it is unknown if PM exposure could affect the population of bone marrow stem cells (BMSCs). The present study was to investigate the effects of PM on BMSCs population and related mechanism(s).Main MetheodsPM was intranasally distilled into male C57BL/6 mice for one month. Flow cytometry with antibodies for BMSCs, Annexin V and BrdU ware used to determine the number of BMSCs and the levels of their apoptosis and proliferation in vivo. Phosphorylated Akt (P-Akt) level was determined in the BM cells with western blotting. Intracellular reactive oxygen species (ROS) formation was quantified using flow cytometry analysis. To determine the role of PM-induced ROS in BMSCs population, proliferation, and apotosis, experiments were repeated using N-acetylcysteine (NAC)-treated wild type mice or a triple transgenic mouse line with overexpression of antioxidant network (AON) composed of superoxide dismutase (SOD)1, SOD3, and glutathione peroxidase-1 with decreased in vivo ROS production.Key FindingsPM treatment significantly reduced BMSCs population in association with increased ROS formation, decreased P-Akt level, and inhibition of proliferation of BMSCs without induction of apoptosis. NAC treatment or AON overexpression with reduced ROS formation effectively prevented PM-induced reduction of BMSCs population and proliferation with partial recovery of P-Akt level.SignificancePM exposure significantly decreased the population of BMSCs due to diminished proliferation via ROS-mediated mechanism (could be partially via inhibition of Akt signaling).
Highlights
A recent Global Burden of Disease Study suggested that the ambient fine particulate matter (PM) PM is responsible for 3.2 million deaths per year and 76 million years of healthy life lost [1]
To determine if the decreased cell population by PM exposure could be due to increased apoptosis, we evaluated the level of apoptosis of bone marrow stem cells (BMSCs)
We demonstrated that PM exposure significantly decreased the BMSCs population in association with inhibition of Akt phosphorylation
Summary
A recent Global Burden of Disease Study suggested that the ambient fine particulate matter (PM) PM is responsible for 3.2 million deaths per year and 76 million years of healthy life lost [1]. The majority of mortality following PM exposure has been shown to be related to cardiovascular diseases [1]. Different sources of PM contain different components. It has been reported that PM exposure is able to produce many deleterious effects on cardiovascular system such as vascular dysfunction, reduced heart rate variability and enhanced coagulation-thrombosis potential [2, 4]. Long-term exposure of PM accelerated the process of atherosclerosis and vascular inflammation in apolipoprotein E-/- mice with high fat diet [5]
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