The plant decapeptide OSIP108 prevents copper-induced apoptosis in yeast and human cells

Abstract

We previously identified the Arabidopsis thaliana–derived decapeptide OSIP108, which increases tolerance of plants and yeast cells to oxidative stress. As excess copper (Cu) is known to induce oxidative stress and apoptosis, and is characteristic for the human pathology Wilson disease, we investigated the effect of OSIP108 on Cu-induced toxicity in yeast. We found that OSIP108 increased yeast viability in presence of toxic Cu concentrations, and decreased the prevalence of Cu-induced apoptotic markers. Next, we translated these results to the human hepatoma HepG2 cell line, demonstrating anti-apoptotic activity of OSIP108 in this cell line. In addition, we found that OSIP108 did not affect intracellular Cu levels in HepG2 cells, but preserved HepG2 mitochondrial ultrastructure. As Cu is known to induce acid sphingomyelinase activity of HepG2 cells, we performed a sphingolipidomic analysis of OSIP108-treated HepG2 cells. We demonstrated that OSIP108 decreased the levels of several sphingoid bases and ceramide species. Moreover, exogenous addition of the sphingoid base dihydrosphingosine abolished the protective effect of OSIP108 against Cu-induced cell death in yeast. These findings indicate the potential of OSIP108 to prevent Cu-induced apoptosis, possibly via its effects on sphingolipid homeostasis.

The Plant Peptidome: An Expanding Repertoire of Structural Features and Biological Functions

“…Both overexpression and infiltration of synthetic OSIP108 in Arabidopsis leaves resulted in increased oxidative stress tolerance. Moreover, treatment of other eukaryotes with OSIP108 was demonstrated to prevent apoptosis triggered by different oxidative stress inducers (Spincemaille et al, 2014a(Spincemaille et al, , 2014b. Although these findings support a function for OSIP108 as a peptide, the latter could not yet be identified as such in planta and its translation can be questioned.…”

Identification of survival-promoting OSIP108 peptide variants and their internalization in human cells

“…OSIP108 is a plant-derived decapeptide with anti-apoptotic properties (Spincemaille et al, 2014b , or a copper-treated U87 glioblastoma cell line (Spincemaille et al, 2014c). We previously also translated these findings to a zebrafish larvae model for Wilson's disease.…”

“…Yeast survival in presence of 1.75 mM CuSO4 upon treatment with either control (2% DMSO) or peptide (100 µM) was evaluated as before (Spincemaille et al, 2014b).…”

“…Viability of HepG2 cells in presence of 0.75 mM CuCl2 treated with either peptide (5 µM-100 µM) or control (1% DMSO) was assessed as previously described (Spincemaille et al, 2014b …”

“…For instance, using a copper-toxicity yeast model for Wilson's disease (Spincemaille et al, 2014b), we have previously identified a potent anti-apoptotic peptide, OSIP108, derived from the plant Arabidopsis thaliana (De Coninck et al, 2013). This decapeptide increases the tolerance of yeast and human cells to apoptosis-inducing compounds such as copper and cisplatin (Spincemaille et al, 2014a(Spincemaille et al, , 2014b.…”