Abstract
Hematopoietic stem cells (HSCs) aging is associated with hematopoietic dysfunction and diseases. Our previous study showed that lead exposure induced a functional decline in HSCs. Allicin, a chemical extracted from the garlic (Allium sativum L.), has been reported to have antioxidative and anti-inflammatory effects. However, the biological activities of allicin on lead-induced toxicity, especially in the hematopoietic system, remain unclear. Here, we found that lead exposure elicited aging phenotypes in HSCs, including perturbed cell quiescence, disabled self-renewal function and colony-forming ability, and myeloid-biased differentiation, all of which contributed to significant hematopoietic disorders in mice. Intragastric administration of allicin substantially ameliorated lead-induced HSCs aging phenotypes in vivo. Lead exposure induced a peroxide condition in HSCs leading to DNA damage, which reduced expression of the glycolytic enzyme pyruvate kinase M2 isoform (PKM2), a phenotype which was significantly ameliorated by allicin treatment. These findings suggested that allicin alleviated lead-induced HSCs aging by up-regulating PKM2 expression; thus, it could be a natural herb for preventing lead toxicity.
Highlights
Aging is a physiological process that is driven by both intrinsic and extrinsic factors
Consistent with previous studies [8], we found that lead exposure led to a significant reduction in white blood cells (WBCs) (Figure 1A), red blood cells (RBCs) (Figure 1B) and hemoglobin (Figure 1C)
Organismal aging is associated with chronic low-grade inflammatory senescence-associated secretory phenotype (SASP), and inflammatory factors IL-6 and TNF-α are the biomarkers of SASP [24,25]
Summary
Aging is a physiological process that is driven by both intrinsic and extrinsic factors. Hematopoietic stem cells (HSCs), the common progenitor of all blood cells, comprise one of the best characterized stem cell populations in the body and the only stem cell that is clinically applied for disease treatment, such as breast cancer, leukemia, and congenital immunodeficiencies [1]. It has been reported that the capacity to generate lymphoid cells declines as HSCs age, and impaired hematopoietic systems are observed in aged mice [2], which show enhanced myelopoiesis and suppressed lymphoid lineages [3]. HSCs aging is implicated in chronic inflammation, and declined immune function, which leads to the onset of serious diseases [4]. Previous studies have identified that the hematological system is an important target of lead-induced toxicity, and that lead exposure impairs HSCs function by inducing HSCs aging or apoptosis [8]. Dysfunctional HSCs result from an imbalance in erythrocytes, while due to the fact that erythrocytes exist in the various organs of the body, their status will affect other systems [9]
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