The Promotion of Erythropoiesis via the Regulation of Reactive Oxygen Species by Lactic Acid.
The simultaneous increases in blood lactic acid and erythrocytes after intense exercise could suggest a link between lactate and the erythropoiesis. However, the effects of lactic acid on erythropoiesis remain to be elucidated. Here, we utilized a mouse model to determine the role of lactic acid in this process in parallel with studies using leukaemic K562 cells. Treatment of K562 cells in vitro with lactic acid increased the mRNA and protein expression of haemoglobin genes and the frequency of GPA+cells. Also, increases in haematocrit and CD71-/Ter119+erythroid cells were observed in lactic acid-treated mice, which showed a physiological increase in blood lactate. Mouse bone marrow CD34+/CD117-cells showed an increase in erythroid burst-forming units after stimulation with lactic acid in vitro. Furthermore, lactic acid increased the intracellular reactive oxygen species (ROS) content in bone marrow and in K562 cells. Erythroid differentiation induced in Haematopoietic Stem Cells (HSCs) and K562 cells by lactic acid was abolished by reducing ROS levels with SOD or 2-mercaptoethanol, which suggests that ROS is a critical regulator of this process. These findings provide a better understanding of the role of lactic acid in cellular metabolism and physiological functions.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610064, China.
Shun-Tao
ST
Luo
Center of Reproductive Medicine, Department of Gynecology and Obstetrics, State Key Laboratory of Biotherapy, West China Second Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, China.
Dong-Mei
DM
Zhang
Department of Oncology, Chengdu Shang Jin Nan Fu Hospital, Chengdu, Sichuan 610041, China.
Qing
Q
Qin
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610064, China.
Lian
L
Lu
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610064, China.
Min
M
Luo
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610064, China.
Fu-Chun
FC
Guo
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, and Head and Neck Oncology Department of Cancer Center, West China Hospital, Chengdu, 610064, China.
Hua-Shan
HS
Shi
West China Hospital, West China Medical School, Sichuan University, Chengdu, 610064, China.
Li
L
Jiang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610064, China.
Bin
B
Shao
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610064, China.
Meng
M
Li
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610064, China.
Han-Shuo
HS
Yang
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, 610064, China.
Yu-Quan
YQ
Wei
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D015672:Erythroid Precursor Cells / Q000187:drug effects; D004920:Erythropoiesis / Q000187:drug effects*; D005260:Female; D015870:Gene Expression; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000378:metabolism; D006454:Hemoglobins / Q000235:genetics; D006801:Humans; D020014:K562 Cells; D019344:Lactic Acid / Q000378:metabolism / Q000494:pharmacology*; D008807:Mice, Inbred BALB C; D017382:Reactive Oxygen Species / Q000378:metabolism*
D006454:Hemoglobins; D017382:Reactive Oxygen Species; D019344:Lactic Acid