Protective Effect of Nervonic Acid Against 6-Hydroxydopamine-Induced Oxidative Stress in PC-12 Cells.

Increased oxidative stress in the human brain is observed in neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD), and is considered to be a major cause of progression of these disease states. A very long-chain fatty acid, nervonic acid (NA), is the main fatty acid found in various sphingolipid species in the central nervous system. NA plays an important role in forming the plasma membrane's lipid bilayer and in maintaining normal myelin function. In this study, we examined the neuroprotective effect of NA against rat pheochromocytoma (PC-12) cells stimulated by 6-hydroxydopamine (6-OHDA), which served as a cell model of PD. PC-12 cells were pre-treated with different concentrations of NA for 48 h then subsequently co-treated with NA and 6-OHDA for 48 h to induce cellular oxidative stress. Cell viability was significantly increased by pre-treatment with a very low concentration of NA. The level of malondialdehyde, a marker of lipid peroxidation, was significantly decreased in NA-treated cells. The expression levels of superoxide dismutases (Mn SOD and Cu/Zn SOD) and γ-glutamylcysteine synthetase (GCLC), responsible for the synthesis of glutathione, were significantly increased, indicating that pre-treatment with NA activated the cellular antioxidant defense system. These results suggest that NA may play a role as a neuroprotective mediator in the brain.

Fermentative production of nervonic acid by Mortierella capitata RD000969.

A high-nervonic acid (cis-15-tetracosenoic acid, C24:1, n-9)-producing filamentous fungus of the Mortierella species was discovered among soil filamentous fungi. The filamentous fungal strain -RD000969- was isolated from soil collected in Kanagawa Prefecture (Japan) and was found to accumulate nervonic acid at a rate of 6.94% of the total cellular fatty acids. The base sequences of 28S rDNA D1/D2 and ITS 5.8S rDNA showed 100% homology with Mortierella capitata CBS 293.96. In addition to nervonic acid, strain RD000969 produced a large amount of long-chain monounsaturated fatty acids (C20:1, 12.22%; C22:1, 4.07%; C26:1, 5.91%) and a small amount of ultra-long-chain fatty acids (C28:1, 0.44%; C30:1, 0.06%; C32:1, trace). In the fungal cells, 98.87% of nervonic acid was localized at the sn-1,3 position of triacylglycerol. Nervonic acid production was maximum (186.3 mg·L(-1)) when the fungus was cultured in potato dextrose (PD) medium containing yeast extract, CaCl2, and MgSO4·7H2O.