Sulforaphane (SFN), an isothiocyanate compound that is formed in the breakdown process of cruciferous vegetables, has demonstrated the ability to interfere with dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. The present study investigated whether SFN can protect cells exhibiting persistent mitochondrial fission induced by nitrosative stress (S- nitrosoglutathione; GSNO), and shed light on the mechanism by which this occurs. Results show that SFN (5 μM) prevents decreases in the rate of mitochondrial oxidative phosphorylation (ATP production) in SH-SY5Y neuroblastoma cells treated with 200-600 μM GSNO, which was associated with significant improvements in cell viability at all doses. Based upon the understood activation mechanism of Drp1, we further explored the possibility that SFN interferes with phosphorylation of Drp1 at serine residue 616 (pDrp1-Ser616). Indeed, SFN significantly reduced GSNO-mediated increases in pDrp1-Ser616, suggesting a possible mechanism of cytoprotection. However, due to the various reported targets of SFN, it remains unclear if SFN interferes directly with Drp1 phosphorylation or with other targets upstream of this event.
|Commitee:||Chicco, Adam J., Legare, Marie E.|
|School:||Colorado State University|
|Department:||Environmental and Radiological Health Sciences|
|School Location:||United States -- Colorado|
|Source:||MAI 58/06M(E), Masters Abstracts International|
|Subjects:||Toxicology, Biochemistry, Aging|
|Keywords:||Dynamin-related protein, Mitochondrial fission, Neurodegeneration, Nitric oxide, Sulforaphane|
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