A novel nonapeptide SSDAFFPFR from Antarctic krill exerts a protective effect on PC12 cells through the BCL-XL/Bax/Caspase-3/p53 signaling pathway

This study aims to investigate the protective effect on PC12 cells of Ser-Ser-Asp-Ala-Phe-Phe-Pro-Phe-Arg(SSDAFFPFR) and Ser-Asn-Val-Phe-Asp-Met-Phe (SNVFDMF) derived from Antarctic krill and the related signaling pathways involved in the inhibition of oxidative stress. Peptide sequences of the antioxidant component in the hydrolysates of Antarctic krill were identified by Nano-HPLC- MS/MS, then the bioactivity was predicted by in silico analysis. Results showed that SSDAFFPFR and SNVFDMF showed the highest activity with a PeptideRanker score of 0.97 and 0.89, respectively, and both contained serine and phenylalanine related to the antioxidant activity. Based on Electron paramagnetic resonance (EPR) method, SSDAFFPFR exhibited a higher DPPH radical scavenging rate than SNVFDMF (71.88 ± 4.01% vs 34.57 ± 2.38%), due to the presence of hydroxyl, amino, and carboxyl groups at its C and N terminals as well as the branched-chain of SSDAFFPFR peptide. In addition, SSDAFFPFR significantly suppressed the decrease of SOD activity and decreased ROS content induced by scopolamine in PC12 cells, as well as inhibited the expression of Bax, Caspase-3 and p53 and promoted the expression of BCL-XL, thereby protecting PC12 cells from the effects of oxidative stress. Thus the Antarctic krill peptide SSDAFFPFR showed its protective effect on PC12 cells through the BCL-XL/Bax/Caspase-3/p53 pathway.