High-volume endurance exercise training stimulates hematopoiesis by increasing ACE NH2-terminal activity

Author(s)

Magalhaes, Flavio de Castro ^{[1, 2]} ; Fernandes, Tiago ^[1] ; Bassaneze, Vinicius ^[3] ; Mattos, Katt Coelho ^[1] ; Schettert, Isolmar ^[3] ; Navarro Marques, Fabio Luiz ^[4] ; Krieger, Jose Eduardo ^[3] ; Nava, Roberto ^[5] ; Barauna, Valerio Garrone ^[6] ; de Oliveira, Edilamar Menezes ^[1]

Affiliation

^[1] Univ Sao Paulo, Sch Phys Educ & Sport, Lab Biochem Motor Act, Sao Paulo - Brazil

^[2] Fed Univ Jequitinhonha & Mucuri Valleys, Integrated Ctr Hlth Res, Lab Exercise Biol, Programa Multicentr Posgrad Ciencias, 5000 MGT 367 Rd Km 583 Alto da Jacuba, BR-39100000 Diamantina, MG - Brazil

^[3] Univ Sao Paulo, Med Sch, Heart Inst Incor, Lab Genet & Mol Cardiol, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Nucl Med Ctr, Med Sch, Radiopharm Lab, Sao Paulo - Brazil

^[5] Univ New Mexico, Dept Hlth Exercise & Sports Sci, Albuquerque, NM 87131 - USA

^[6] Univ Fed Espirito Santo, Hlth Sci Ctr, Lab Mol & Cellular Physiol, Vitoria, ES - Brazil

• Document type: Journal article
• Source: Clinical Science; v. 135, n. 20, p. 2377-2391, OCT 2021.
• Web of Science Citations: 0

Abstract

One of the health benefits of endurance exercise training (ET) is the stimulation of hematopoiesis. However, the mechanisms underlying ET-induced hematopoietic adaptations are understudied. N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (Ac-SDKP) inhibits proliferation of early hematopoietic progenitor cells. The angiotensin I-converting enzyme (ACE) NH2-terminal promotes hematopoiesis by inhibiting the anti-hematopoietic effect of Ac-SDKP. Here we demonstrate for the first time the role of ACE NH2-terminal in ET-induced hematopoietic adaptations. Wistar rats were subjected to 10 weeks of moderate-(T1) and high-(T2) volume swimming-training. Although both protocols induced classical ET-associated adaptations, only T2 increased plasma ACE NH2-domain activity (by 40%, P=0.0003) and reduced Ac-SDKP levels (by 50%, P<0.0001). T2 increased the number of hematopoietic stem cells (HSCs; similar to 200%, P=0.0008), early erythroid progenitor colonies (similar to 300%, P<0.0001) and reticulocytes (similar to 500%, P=0.0007), and reduced erythrocyte lifespan (similar to 50%, P=0.022). Following, Wistar rats were subjected to T2 or T2 combined with ACE NH2-terminal inhibition (captopril (Cap) treatment: 10 mg.kg(-1).day(-1)). T2 combined with ACE NH2-terminal inhibition prevented Ac-SDKP decrease and attenuated ET-induced hematopoietic adaptations. Altogether, our findings show that ET-induced hematopoiesis was at least partially associated with increased ACE NH2-terminal activity and reduction in the hematopoietic inhibitor Ac-SDKP. (AU)