Attenuated SUMOylation of sirtuin 1 in premature neonates with bronchopulmonary dysplasia

A prospective study was performed to investigate the effects of hyperoxia on the expression of small ubiquitin-related modifier (SUMO) and sirtuin 1 (SIRT1) proteins, and to examine interactions between these proteins in premature neonates with bronchopulmonary dysplasia (BPD). Peripheral blood mononuclear cells (PBMCs) were isolated from residual venous blood samples of 20 premature infants with BPD and 20 gender-matched premature infants without BPD (non-BPD group). Expression levels of SUMO and SIRT1 proteins in PBMCs were assessed by western blot analysis, and their interactions in PBMCs were detected using the immunoprecipitation assay. Based on the fraction of inspired oxygen (FiO(2)) administered, neonates were divided into normoxia, low-(21%<30%), medium-(30%FiO(2)<40%) and high-oxygen (FiO(2)40%) groups. Expression levels of SUMO1 and SUMO2/3 proteins in the normoxia group were significantly lower than those in the medium- or high-oxygen groups (P<0.01), but were comparable to those in the low-oxygen group. SIRT1 expression levels in both the medium- and high-oxygen groups were significantly lower than those in the normoxia group (P<0.01). In the BPD group, the expression of SIRT1 protein was significantly lower (P<0.01), and its interaction with SUMO1 and SUMO2/3 was significantly attenuated compared with that in the non-BPD group (P<0.01). Supplemental oxygen with FiO(2)30% was associated with upregulation of SUMO1 and SUMO2/3 expression and downregulation of SIRT1 expression. The present findings suggest that decreased SIRT1 expression and its SUMOylation by SUMO1 and SUMO2/3 may be associated with the development of BPD.