Abstract
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.
Highlights
Congenital heart disease (CHD) is a common congenital malformation that endangers the life and health of newborn babies and accounts for the highest incidence of birth defects in infants [1]
The results showed that the level of SUMO1-modified protein was decreased during embryonic cardiac development (Fig 1A)
The results indicate that the SUMOylation and deSUMOylation were maintained in a dynamic balance, and the levels of SUMOylated proteins were gradually decreased with the maturation of myocardium and cardiac growth
Summary
Congenital heart disease (CHD) is a common congenital malformation that endangers the life and health of newborn babies and accounts for the highest incidence of birth defects in infants [1]. It is believed that genetic and environmental factors are involved in the occurrence of CHD. Heart development is a sophisticated process controlled by multiple transcription factor families, such as myocyte enhancer factor-2. Zinc deficiency induces myocardial abnormalities via SENP5 overexpression.
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