Role of DNMT3a in Hydroquinone-Induced Hematopoietic Stem Cell Toxicity.
10.19746/j.cnki.issn.1009-2137.2022.02.047
- Author:
Kun WU
1
;
Bo NIE
2
;
Jin-Rong YANG
2
;
Zheng-Xin HE
2
;
Shen-Ju CHENG
1
;
Yan-Hong LI
1
;
Zhen JIN
3
;
Ming-Xia SHI
4
Author Information
1. Department of Clinical Laboratory (Yunnan Key Laboratory of Laboratory Medicine, Yunnan Innovation Team of Clinical Laboratory and Diagnosis), The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
2. Department of Hematology (Yunnan Provincial Research Center for Hematology), The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China.
3. Department of Clinical Laboratory (Yunnan Key Laboratory of Laboratory Medicine, Yunnan Innovation Team of Clinical Laboratory and Diagnosis), The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China,E-mail：jinzhen@ydyy.cn.
4. Department of Hematology (Yunnan Provincial Research Center for Hematology), The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China,E-mail: shmxia2002@sina.com.
- Publication Type:Journal Article
- Keywords:
DNMT3a;
PARP-1;
apoptosis;
hematopoietic stem cell;
hydroquinone;
morphology
- MeSH:
Apoptosis;
Cell Proliferation;
DNA Methyltransferase 3A;
Hematopoietic Stem Cells/drug effects*;
Humans;
Hydroquinones/toxicity*;
Poly (ADP-Ribose) Polymerase-1;
RNA, Messenger/metabolism*
- From:
Journal of Experimental Hematology
2022;30(2):607-612
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To investigate the regulatory effect and mechanism of DNA methyltransferase 3A (DNMT3a) in hydroquinone-induced hematopoietic stem cell toxicity.
METHODS:Cells (HSPC-1) were divided into 4 groups, that is A: normal HSPC-1; B: HQ-intervented HSPC-1; C: group B + pcDNA3 empty vector; D: group B + pcDNA3- DNMT3a. RT-qPCR and Western blot were used to detect the expression levels of DNMT3a and PARP-1 mRNA and protein, respectively. Cell morphology was observe; Cell viability and apoptosis rate of HSPC-1 were detected by MTT and flow cytometry, respectively.
RESULTS:Compared with group A, the expression levels of DNMT3a mRNA and protein in HSPC-1 of group B were decreased, while PARP-1 mRNA and protein were increased (P<0.05); there was no significant difference in the above indexes between group C and group B; compared with group B, the expression levels of DNMT3a mRNA and protein showed increased, while PARP-1 mRNA and protein were decreased significantly in cells of group D transfected with DNMT3a (P<0.05). Cells in each group were transfected with DNMT3a and cultured for 24 h, HSPC-1 in group A showed high density growth and mononuclear fusion growth, while the number of HSPC-1 in group B and C decreased and grew slowly. Compared with group B and C, the cell growth rate of group D was accelerated. The MTT analysis showed that cell viability of HSPC-1 in group B were lower than that of group A at 24 h, 48 h and 72 h (P<0.05); after transfected with DNMT3a, the cell viability of HSPC-1 in group D were higher than that of group B at 24 h, 48 h and 72 h (P<0.05). The apoptosis rate of cells in group B was significantly higher than that of group A (P<0.001), while the apoptosis rate in group D was lower than that of group B (P<0.001).
CONCLUSION:DNMT3a may be involved in the damage of hematopoietic stem cells induced by hydroquinone, which may be related to the regulation of PARP-1 activity by hydroquinone-inhibited DNMT3a.
