Open AccessZinc deficiency induces abnormal development of the myocardium by promoting SENP5 overexpression
Author(s) -
Xiaoyu Zhang,
Cuancuan Wang,
Dan Zhao,
Xuhong Chen,
Chunyan Zhang,
Jun Zheng,
Xiao-zhi Liu
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0242606
Subject(s) - zinc deficiency (plant disorder) , apoptosis , proteases , biology , transfection , small interfering rna , microbiology and biotechnology , zinc finger , medicine , endocrinology , zinc , cancer research , chemistry , enzyme , biochemistry , gene , transcription factor , organic chemistry
Gestational zinc deficiency is a cause of congenital heart disease in the fetus, and sentrin/small ubiquitin-like modifier (SUMO)-specific proteases (SENPs) as deSUMOylation enzymes play a crucial role in the development of cardiac structures. However, current studies of the regulation and function of SENP in zinc-deficient status during heart development remain limited. In this study, SUMO1 modification was found to gradually decrease during heart development, and the level of SENP5 exhibited a similar trend to SUMO1 conjugation. In addition, zinc deficiency resulted in cardiac dysplasia, increased cell apoptosis, decreased cell viability, and differentiation inhibition of hiPSC-CMs. In order to investigate the function of SENP5 in zinc deficiency, hiPSC-CMs were transfected with SENP5 small interfering RNA. The negative effects of zinc lacking conditions were reversed with depletion of SENP5. It was confirmed that zinc deficiency induced abnormal differentiation of hiPSCs and increased apoptosis of hiPSC-CMs by promoting SENP5 overexpression, which led to cardiac dysplasia. Thus, it was concluded that SENP5 regulates the SUMO1 deconjugation during heart development and zinc deficiency may reduce conjugated SUMO by promoting SENP5 overexpression, which induces abnormal development of the myocardium.