Carnosic acid attenuated 6-hydroxydopamine-induced apoptosis through mediation of the mitochondrial biogenesis by parkin in SH-SY5Y cells

[Speaker] Chia-Wen Tsai:1
[Co-author] Yan-Ning Huang:1, Chia-Yuan Lin:1
1:Department of Nutrition, China Medical University, Taiwan.

C.W. Tsai E-mail:
 Background: Impaired mitochondrial biogenesis is associated with the pathogenesis of Parkinson's disease (PD). Carnosic acid (CA) is a rosemary diterpene, has neuroprotective effects. We investigated whether CA against the mitochondrial biogenesis impairment of 6-OHDA is mediated via regulating parkin interacting substrate (PARIS) and peroxisome proliferator-activated receptor γ coctivator-1 alpha (PGC-1α) by parkin in human SH-SY5Y cells.
 Methods: The protein expression was measured using Western blotting. The method of small RNA interference transfection was used to explore the effect of knockdown of parkin and PGC-1α.
 Results: Cells treated with 6-OHDA decreased the protein expression of nuclear respiratory factor 1 (NRF1) and mitochondria transcription factor A (TFAM), however, CA pretreatment normalized these protein. 6-OHDA increased the PARIS protein at 3-6 h and decreased the PGC-1α protein up to 12 h. In contrast, cells cultured with CA increased the protein expression of PGC-1α. The induction of PARIS protein and the reduction of PGC-1α by 6-OHDA was reversed in the presence of CA. Suppression of parkin attenuated the ability of CA to reverse the effects of 6-OHDA on PARIS induction and PGC-1α inhibition. In cells-treated with PGC-1α siRNA, CA could no longer significantly reverse the reduction of PGC-1α, NRF1, and TFAM, as well as the induction of apoptotic proteins by 6-OHDA.
 Conclusion: The attenuation of 6-OHDA-induced apoptosis by CA is related to the enhancement of mitochondrial biogenesis via inhibiting PARIS and up-regulating PGC-1α by parkin.

Keywords: Carnosic acid, Parkinson's disease, mitochondrial biogenesis

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