N‐acetylcysteine prevents oxidized low‐density lipoprotein‐induced reduction of MG53 and enhances MG53 protective effect on bone marrow stem cells

Abstract MG53 is an important membrane repair protein and partially protects bone marrow multipotent adult progenitor cells (MAPCs) against oxidized low‐density lipoprotein (ox‐LDL). The present study was to test the hypothesis that the limited protective effect of MG53 on MAPCs was due to ox‐LDL‐induced reduction of MG53. MAPCs were cultured with and without ox‐LDL (0‐20 μg/mL) for up to 48 hours with or without MG53 and antioxidant N‐acetylcysteine (NAC). Serum MG53 level was measured in ox‐LDL‐treated mice with or without NAC treatment. Ox‐LDL induced significant membrane damage and substantially impaired MAPC survival with selective inhibition of Akt phosphorylation. NAC treatment effectively prevented ox‐LDL‐induced reduction of Akt phosphorylation without protecting MAPCs against ox‐LDL. While having no effect on Akt phosphorylation, MG53 significantly decreased ox‐LDL‐induced membrane damage and partially improved the survival, proliferation and apoptosis of MAPCs in vitro. Ox‐LDL significantly decreased MG53 level in vitro and serum MG53 level in vivo without changing MG53 clearance. NAC treatment prevented ox‐LDL‐induced MG53 reduction both in vitro and in vivo. Combined NAC and MG53 treatment significantly improved MAPC survival against ox‐LDL. These data suggested that NAC enhanced the protective effect of MG53 on MAPCs against ox‐LDL through preventing ox‐LDL‐induced reduction of MG53..

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:24

Enthalten in:

Journal of Cellular and Molecular Medicine - 24(2020), 1, Seite 886-898

Beteiligte Personen:

Li, Xin [VerfasserIn]
Jiang, Meng [VerfasserIn]
Tan, Tao [VerfasserIn]
Narasimhulu, Chandrakala A. [VerfasserIn]
Xiao, Yuan [VerfasserIn]
Hao, Hong [VerfasserIn]
Cui, Yuqi [VerfasserIn]
Zhang, Jia [VerfasserIn]
Liu, Lingjuan [VerfasserIn]
Yang, Chunlin [VerfasserIn]
Li, Yixi [VerfasserIn]
Ma, Jianjie [VerfasserIn]
Verfaillie, Catherine M. [VerfasserIn]
Parthasarathy, Sampath [VerfasserIn]
Zhu, Hua [VerfasserIn]
Liu, Zhenguo [VerfasserIn]

BKL:

44.46

Anmerkungen:

Copyright © 2020 Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine

Umfang:

13

doi:

10.1111/jcmm.14798

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

WLY008005931