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Mech Ageing Dev. 2017 Jan;161(Pt B):247-254. doi: 10.1016/j.mad.2016.07.013. Epub 2016 Aug 1.

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

Author information

1
Centre of Microbial and Plant Genetics, CMPG, KU Leuven, Kasteelpark Arenberg 20, box 2460, 3001 Leuven, Belgium.
2
Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia.
3
Centre of Microbial and Plant Genetics, CMPG, KU Leuven, Kasteelpark Arenberg 20, box 2460, 3001 Leuven, Belgium; Department of Laboratory Medicine, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
4
Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster, Germany.
5
Centre of Microbial and Plant Genetics, CMPG, KU Leuven, Kasteelpark Arenberg 20, box 2460, 3001 Leuven, Belgium; Department of Plant Systems Biology, VIB, Technologiepark 927, 9052 Ghent, Belgium.
6
Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
7
Centre of Microbial and Plant Genetics, CMPG, KU Leuven, Kasteelpark Arenberg 20, box 2460, 3001 Leuven, Belgium; Department of Plant Systems Biology, VIB, Technologiepark 927, 9052 Ghent, Belgium. Electronic address: bruno.cammue@biw.kuleuven.be.

Abstract

The plant-derived decapeptide OSIP108 increases tolerance of yeast and human cells to apoptosis-inducing agents, such as copper and cisplatin. We performed a whole amino acid scan of OSIP108 and conducted structure-activity relationship studies on the induction of cisplatin tolerance (CT) in yeast. The use of cisplatin as apoptosis-inducing trigger in this study should be considered as a tool to better understand the survival-promoting nature of OSIP108 and not for purposes related to anti-cancer treatment. We found that charged residues (Arg, His, Lys, Glu or Asp) or a Pro on positions 4-7 improved OSIP108 activity by 10% or more. The variant OSIP108[G7P] induced the most pronounced tolerance to toxic concentrations of copper and cisplatin in yeast and/or HepG2 cells. Both OSIP108 and OSIP108[G7P] were shown to internalize equally into HeLa cells, but at a higher rate than the inactive OSIP108[E10A], suggesting that the peptides can internalize into cells and that OSIP108 activity is dependent on subsequent intracellular interactions. In conclusion, our studies demonstrated that tolerance/survival-promoting properties of OSIP108 can be significantly improved by single amino acid substitutions, and that these properties are dependent on (an) intracellular target(s), yet to be determined.

KEYWORDS:

Apoptosis-inducers; Cellular internalization; OSIP108; Structure activity relationship study; Survival

PMID:
27491841
DOI:
10.1016/j.mad.2016.07.013
[Indexed for MEDLINE]

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