AIMS: A component of the base excision repair pathway, poly(ADP-ribose) polymerase-1 (PARP1) functions in multiple cellular processes, including DNA repair and programmed cell death. We previously showed that Salidroside, a phenylpropanoid glycoside isolated from medicinal plants, prevented the loss of hematopoietic stem cells (HSCs) in native mice and rescued HSCs repopulating in transplanted recipients under oxidative stress. The aim of this study was to investigate the mechanism by which PARP1 activation by Salidroside maintains HSCs under oxidative stress. RESULTS: We found that although there were no spontaneous defects in hematopoiesis in Parp1(-/-) mice, oxidative stress compromised the repopulating capacity of Parp1(-/-) HSCs in transplanted recipient mice. A biochemical study using truncated proteins lacking the defined functional domains of PARP1 showed that the tryptophan-glycine-arginine-rich (WGR) domain of PARP1 was critical for Salidroside binding and subsequent PARP1 activation under oxidative stress. Functionally, complementation of Parp1(-/-) HSCs with full-length PARP1WT, but not the PARP1R591K mutant in WGR domain restored Salidroside-stimulated PARP1 activation in vitro. Mechanistically, activated PARP1 by Salidroside enhanced the repopulating capacity of the stressed HSCs by accelerating oxidative DNA damage repair. INNOVATIONS AND CONCLUSION: Our findings reveal the action of mechanism for Salidroside in PARP1 stimulation and a novel role of PARP1 activation in maintaining HSC function under oxidative stress.
AIMS: A component of the base excision repair pathway, poly(ADP-ribose) polymerase-1 (PARP1) functions in multiple cellular processes, including DNA repair and programmed cell death. We previously showed that Salidroside, a phenylpropanoid glycoside isolated from medicinal plants, prevented the loss of hematopoietic stem cells (HSCs) in native mice and rescued HSCs repopulating in transplanted recipients under oxidative stress. The aim of this study was to investigate the mechanism by which PARP1 activation by Salidroside maintains HSCs under oxidative stress. RESULTS: We found that although there were no spontaneous defects in hematopoiesis in Parp1(-/-) mice, oxidative stress compromised the repopulating capacity of Parp1(-/-) HSCs in transplanted recipient mice. A biochemical study using truncated proteins lacking the defined functional domains of PARP1 showed that the tryptophan-glycine-arginine-rich (WGR) domain of PARP1 was critical for Salidroside binding and subsequent PARP1 activation under oxidative stress. Functionally, complementation of Parp1(-/-) HSCs with full-length PARP1WT, but not the PARP1R591K mutant in WGR domain restored Salidroside-stimulated PARP1 activation in vitro. Mechanistically, activated PARP1 by Salidroside enhanced the repopulating capacity of the stressed HSCs by accelerating oxidative DNA damage repair. INNOVATIONS AND CONCLUSION: Our findings reveal the action of mechanism for Salidroside in PARP1 stimulation and a novel role of PARP1 activation in maintaining HSC function under oxidative stress.
Authors: Anne Wilson; Elisa Laurenti; Gabriela Oser; Richard C van der Wath; William Blanco-Bose; Maike Jaworski; Sandra Offner; Cyrille F Dunant; Leonid Eshkind; Ernesto Bockamp; Pietro Lió; H Robson Macdonald; Andreas Trumpp Journal: Cell Date: 2008-12-12 Impact factor: 41.582
Authors: C J Cairney; G Sanguinetti; E Ranghini; A D Chantry; M C Nostro; A Bhattacharyya; C N Svendsen; W N Keith; I Bellantuono Journal: Biochim Biophys Acta Date: 2009-02-06
Authors: Xiaoling Zhang; Xun Shang; Fukun Guo; Kim Murphy; Michelle Kirby; Patrick Kelly; Lilith Reeves; Franklin O Smith; David A Williams; Yi Zheng; Qishen Pang Journal: Blood Date: 2008-06-18 Impact factor: 22.113
Authors: Noha A S Al-Otaibi; Juliana S Cassoli; Daniel Martins-de-Souza; Nigel K H Slater; Hassan Rahmoune Journal: Gigascience Date: 2019-03-01 Impact factor: 6.524