Allicin alleviates lead-induced hematopoietic stem cell aging by up-regulating PKM2

Biosci Rep. 2019 Jul 5;39(7):BSR20190243. doi: 10.1042/BSR20190243. Print 2019 Jul 31.

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.

Keywords: Aging; Allicin; Hematopoietic stem cell; Lead; PKM2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / drug effects
  • Aging / genetics*
  • Aging / pathology
  • Animals
  • Antioxidants / pharmacology
  • Cell Proliferation / drug effects
  • DNA Damage / drug effects
  • Disulfides
  • Gene Expression Regulation, Developmental
  • Hematopoietic Stem Cells / drug effects*
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Mice
  • Protein Isoforms / genetics
  • Pyruvate Kinase / genetics*
  • Sulfinic Acids / pharmacology*

Substances

  • Antioxidants
  • Disulfides
  • Protein Isoforms
  • Sulfinic Acids
  • allicin
  • Pkm protein, mouse
  • Pyruvate Kinase