title: Salidroside stimulates DNA repair enzyme Parp-1 activity in mouse HSC maintenance.
abstract: Salidroside is a phenylpropanoid glycoside isolated from the medicinal plant Rhodiola rosea, which has potent antioxidant properties. Here we show that salidroside prevented the loss of hematopoietic stem cells (HSCs) in mice under oxidative stress. Quiescent HSCs were recruited into cell cycling on in vivo challenge with oxidative stress, which was blocked by salidroside. Surprisingly, salidroside does not prevent the production of reactive oxygen species but reduces hydrogen peroxide-induced DNA-strand breaks in bone marrow cells enriched for HSCs. We tested whether salidroside enhances oxidative DNA damage repair in mice deficient for 5 DNA repair pathways known to be involved in oxidative DNA damage repair; we found that salidroside activated poly(ADP-ribose)polymerase-1 (PARP-1), a component of the base excision repair pathway, in mouse bone marrow HSCs as well as primary fibroblasts and human lymphoblasts. PARP-1 activation by salidroside protects quiescent HSCs from oxidative stress-induced cycling in native animals and self-renewal defect in transplanted recipients, which was abrogated by genetic ablation or pharmacologic inhibition of PARP-1. Together, these findings suggest that activation of PARP-1 by salidroside could affect the homeostasis and function of HSCs and contribute to the antioxidant effects of salidroside.
authors.affiliation: Division of Experimental Hematology and Cancer Biology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Ave, Cincinnati, OH 45229, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Jared
authors.initials: J
authors.lastname: Sipple
authors.forename: Qishen
authors.initials: Q
authors.lastname: Pang
authors.forename: Wei
authors.initials: W
authors.lastname: Du
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D004247:DNA / Q000187:drug effects; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000187:drug effects*; D004353:Drug Evaluation, Preclinical; D052217:Fanconi Anemia Complementation Group A Protein / Q000172:deficiency; D052218:Fanconi Anemia Complementation Group C Protein / Q000172:deficiency; D005960:Glucosides / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D010636:Phenols / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D017382:Reactive Oxygen Species; D029771:Rhodiola / Q000737:chemistry
chemical_list: D000975:Antioxidants; C120277:Fanca protein, mouse; C497652:Fancc protein, mouse; D052217:Fanconi Anemia Complementation Group A Protein; D052218:Fanconi Anemia Complementation Group C Protein; D005960:Glucosides; D016877:Oxidants; D010636:Phenols; D017382:Reactive Oxygen Species; D004247:DNA; D006861:Hydrogen Peroxide; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C009172:rhodioloside