Protective effect and mechanism of rat recombinant S100 calcium‑binding protein A4 on oxidative stress injury of rat vascular endothelial cells

Abstract

The aim of the present study was to examine the protective effects and mechanisms of S100 calcium-binding protein A4 (S100A4) on endothelial cell apoptosis induced by oxidative stress injury. Endothelial cells were cultured and divided into control and oxidative stress injury groups, with the latter state induced by H2O2. Endothelial cells in every group were incubated with or without 50 or 100 µM S100A4. The cell viability and amounts of malondialdehyde, nitric oxide and lactate dehydrogenase in the culture medium were measured. The apoptotic index was detected by TUNEL staining. Western blot and immunoprecipitation analyses were used to detect the expression levels and the association between S100A4 and P53. H2O2 treatment led to oxidative stress injury in the cultured vascular endothelial cells, a decrease in the cell viability and an increase in the rate of apoptosis of vascular endothelial cells compared with the negative control group. Exogenous S100A4 serves a significant function against oxidative stress injury (P<0.05), increasing the viability and attenuating the apoptotic rate of endothelial cells. Western blotting results suggested that the protein levels of S100A4 and P53 increased subsequent to oxidative stress injury and that exogenous S100A4 increased the expression of P53 in the cytoplasm and decreased the expression of P53 in nucleus. The immunoprecipitation assay results revealed a protein-protein interaction between S100A4 and P53. These results suggested that rat recombinant S100A4 serves an anti-apoptotic function in oxidative stress injury. This effect of S100A4 is mediated, at least in part, via the inhibition of the translocation of P53 to the nucleus.

Multi-modal profiling of peripheral blood cells across the human lifespan reveals distinct immune cell signatures of aging and longevity

“…A recent study discovered an S100 protein to be a critical regulator of hematopoietic stem cell renewal through mitochondrial metabolic regulation and function 42 . In rats, recombinant S100A4 demonstrates an anti-apoptotic function in response to oxidative stress injury 43 . Other transcriptional signatures that we identified in our analysis, such as SESN3 and MAP1LC3B (Figure 4E), are involved in DNA damage response and mitochondrial and metabolic regulation activated in response to oxidative stress 29,30 .…”

Mouse aortic biomechanics are affected by short-term defective autophagy in vascular smooth muscle cells

“…While it is mainly the extracellular S100A4 that is related to VSMC phenotype transitions [21,41], the intracellular domain is linked to cell adhesion and matrix remodeling [42,43]. Increase of S100A4 in Atg7 F/F SM22α-Cre + VSMCs, together with previous results by Grootaert et al [8], which showed increased ligationinduced MMP9 activity in Atg7 defective VSMCs, indicate that matrix remodeling could be explained through S100A4 regulated MMP upregulation [9,10,14,18,23,44]. All these parameters are affected by autophagy deficiency in VSMCs, albeit no distinction between extracellular and intracellular S100A4 was made.…”

“…Whether the EC function in 2-month-old Atg7 F/F SM22α-Cre + mouse aorta was enhanced to compensate for altered VSMC function is still unclear. It has been described that S100 proteins are linked to NO release; addition of extracellular S100A4 to rat vascular endothelial cells partially restores decreased NO content after induction of oxidative stress by H 2 O 2 [ 44 ] . Hence, increased synthesis and release of extracellular S100A4 from aortic VSMCs may contribute to the observed enhanced EC function in aorta of young Atg7 F/F SM22α-Cre + mice.…”