Evaluation of the Protective Effects of Sarains on H2O2-Induced Mitochondrial Dysfunction and Oxidative Stress in SH-SY5Y Neuroblastoma Cells.

Abstract

Sarains are diamide alkaloids isolated from the Mediterranean sponge Haliclona (Rhizoniera) sarai that have previously shown antibacterial, insecticidal and anti-fouling activities. In this study, we examined for the first time the neuroprotective effects of sarains 1, 2 and A against oxidative stress in a human neuronal model. SH-SY5Y cells were co-incubated with sarains at concentrations ranging from 0.01 to 10 μM, and the well-known oxidant hydrogen peroxide at 150 μM for 6 h and the protective effects of the compounds were evaluated. Among the sarains tested, sarain A was the most promising compound, improving mitochondrial function and decreasing reactive oxygen species levels in human neuroblastoma cells treated with the compound at 0.01, 0.1 and 1 μM. This compound was also able to increase the activity of the antioxidant enzymes superoxide dismutases by inducing the translocation of the nuclear factor E2-related factor 2 (Nrf2) to the nucleus at the lower concentrations tested (0.01 and 0.1 μM). Moreover, sarain A at 0.1 and 1 μM blocked the mitochondrial permeability transition pore (mPTP) opening through cyclophilin D inhibition. These results suggest that the protective effects produced by the treatment with sarain A are related with its ability to block the mPTP and to enhance the Nrf2 pathway, indicating that sarain A may be a candidate compound for further studies in neurodegenerative diseases.

• Authors: Rebeca Alvariño, Eva Alonso, Marie-Aude Tribalat, Sandra Gegunde, Olivier P Thomas, Luis M Botana
• Journal: Neurotoxicity research (Neurotox Res) Vol. 32 Issue 3 Pg. 368-380 (Oct 2017) ISSN: 1476-3524 [Electronic] United States
• PMID: 28478531 (Publication Type: Journal Article)

Chemical References

• Antioxidants
• Bridged-Ring Compounds
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Neuroprotective Agents
• Reactive Oxygen Species
• sarain A
• Adenosine Triphosphate
• Hydrogen Peroxide
• Cyclophilins
• PPID protein, human

Topics

• Adenosine Triphosphate (metabolism)
• Animals
• Antioxidants (chemistry, isolation & purification, pharmacology)
• Bridged-Ring Compounds (chemistry, isolation & purification, pharmacology)
• Cell Line, Tumor
• Cell Survival (drug effects, physiology)
• Cyclophilins (antagonists & inhibitors, metabolism)
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Haliclona (chemistry)
• Humans
• Hydrogen Peroxide (metabolism, toxicity)
• Membrane Potential, Mitochondrial (drug effects, physiology)
• Mitochondria (drug effects, physiology)
• Mitochondrial Diseases (chemically induced, drug therapy, metabolism)
• NF-E2-Related Factor 2 (metabolism)
• Neurons (drug effects, physiology)
• Neuroprotective Agents (chemistry, isolation & purification, pharmacology)
• Oxidative Stress (drug effects, physiology)
• Reactive Oxygen Species (metabolism)