Parstatin inhibits viability of human retinal pigment epithelium cells: an in vitro cytotoxicity study.

Autor: Gartaganis PS; Department of Pathology, School of Medicine, University of Patras, Patras, Greece. gartaganisp@gmail.com., Cotsiki M, Anastassiou ED, Tsopanoglou NE, Melachrinou MD
Jazyk: angličtina
Zdroj: European review for medical and pharmacological sciences [Eur Rev Med Pharmacol Sci] 2020 May; Vol. 24 (9), pp. 5111-5117.
DOI: 10.26355/eurrev_202005_21204
Abstrakt: Objective: Parstatin, the N-terminal 41-amino-acid peptide cleaved by thrombin from protease-activated-receptor 1, was shown to be highly effective in preventing ocular angiogenesis and as such it has potential therapeutic applications in ocular neovascular diseases. In the frame of a safety program in preclinical development, we investigated whether parstatin exerts any cytotoxic effect in critical ocular cell populations.
Materials and Methods: Human retinal pigment epithelium cell-19 line (ARPE-19) and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay were used to investigate parstatin's effect in cell cultures. Parstatin 24-41 was used as a control peptide which lacks the hydrophobic domain to demonstrate the specificity and the structure-dependent effect of parstatin. Both peptides were used at concentrations ranging from 0.1-30 μM for 24, 48 and 72 hours.
Results: In the presence of parstatin the rate of ARPE-19 cell growth and viability were significantly decreased in a concentration-dependent and time-dependent manner, with an IC50 of approximately 10 μM. When ARPE-19 cells were treated with parstatin 24-41 no inhibitory effect was observed at any concentration or exposure time used.
Conclusions: Parstatin has a clear detrimental effect on the viability of ARPE-19 cells and raises concerns about its use in the eye because of its possible toxic effects.
Databáze: MEDLINE