The therapeutic potential of naturally occurring peptides in counteracting SH-SY5Y cells injury

Perlikowska, Renata; Silva, Joana; Alves, Celso; Susano, Patrícia; Pedrosa, Rui

http://hdl.handle.net/10400.8/8753

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Abstract(s)

Peptides have revealed a large range of biological activities with high selectivity and efficiency for the development of new drugs, including neuroprotective agents. Therefore, this work investigates the neuroprotective properties of naturally occurring peptides, endomorphin-1 (EM-1), endomorphin-2 (EM-2), rubiscolin-5 (R-5), and rubiscolin-6 (R-6). We aimed at answering the question of whether wellknown opioid peptides can counteract cell injury in a common in vitromodel of Parkinson’s disease (PD). Antioxidant activity of these four peptides was evaluated by the 2-diphenyl-1-picrylhydrazyl radical (DPPH) scavenging activity, oxygen radical absorbance capacity (ORAC), and ferric-reducing antioxidant power (FRAP) assays, while neuroprotective effects were assessed in a neurotoxic model induced by 6-hydroxydopamine (6-OHDA) in a human neuroblastoma cell line (SH-SY5Y). The mechanisms associated with neuroprotection were investigated by the determination of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, and Caspase-3 activity. Among the tested peptides, endomorphins significantly prevented neuronal death induced by 6-OHDA treatment, decreasing MMP (EM-1) or Caspase-3 activity (EM-2). Meanwhile, R-6 showed antioxidant potential by FRAP assay and exhibited the highest capacity to recover the neurotoxicity induced by 6-OHDA via attenuation of ROS levels and mitochondrial dysfunction. Generally, we hypothesize that peptides’ ability to suppress the toxic effect induced by 6-OHDA may be mediated by different cellular mechanisms. The protective effect caused by endomorphins results in an antiapoptotic effect (mitochondrial protection and decrease in Caspase-3 activity), while R-6 potency to increase a cell’s viability seems to be mediated by reducing oxidative stress. Our results may provide new insight into neurodegeneration and support the short peptides as a potent drug candidate to treat PD. However, further studies should be conducted on the detailed mechanisms of how tested peptides could suppress neuronal injuries.

Description

This research was funded by the National Science Center (NCN, Miniatura, No DEC-2021/05/X/ST5/00294), PolishNationalAgency forAcademic Exchange (BPN/BPT/2021/1/00053), the Portuguese Foundation for Science and Technology (FCT) through the projects granted to MARE—Marine and Environmental Sciences Centre (UIDP/04292/2020 and UIDB/04292/2020), Associate Laboratory ARNET (LA/P/0069/2020) and CROSS-ATLANTIC (PTDC/BIA-OUT/29250/2017) project, co-financed by European Regional Development Fund (FEDER), through the Operational-Programme for Competitiveness and Internationalization (COMPETE 2020). This study was also supported by Programme for Cooperation in Science between Portugal and Poland through project NEURONS—Natural products as key drivers in the development of nEUropROtective therapeutic ageNtS (FCT/DRI/PNAAE 2021.09608.CBM).

Keywords

Opioid peptides 6-hydroxydopamine Neuronal survival Neuroprotection Antioxidant activity Apoptosis

URI

http://hdl.handle.net/10400.8/8753

Citation

Perlikowska, R.; Silva, J.; Alves, C.; Susano, P.; Pedrosa, R. The Therapeutic Potential of Naturally Occurring Peptides in Counteracting SH-SY5Y Cells Injury. Int. J. Mol. Sci. 2022, 23, 11778. https://doi.org/ 10.3390/ijms231911778