Abstract
Bilobalide (BB), a sesquiterpene trilactone from Ginkgo biloba has been proposed to have protective effects on mitochondrial function. Using ovariectomized rats to mimic the post-menopausal pathophysiological changes in women, this study demonstrated that BB treatment could prevent estrogen withdrawal-induced decrease in mitochondrial adenosine triphosphate content, cytochrome c oxidase subunit I (COXI) mRNA and protein levels and COX activity in hippocampal tissues as effectively as estradiol benzoate. But neither ovariectomy nor BB treatment affected citrate synthase activity. These results suggested that BB was able to regulate COX activity via up-regulation of the gene and protein expression of its mitochondrial DNA-coded subunits, and modulation of COX activity by BB might contribute to its protective effects on mitochondrial function. Given that ovariectomy induces decrease in estrogen levels similar to that of menopause, BB may be useful in developing therapy for neurodegenerative diseases such as Alzheimer’s disease in post-menopausal females.
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References
Benzi G, Pastoris O, Marzatico RF, Villa RF, Curti D (1992) The mitochondrial electron transfer alteration as a factor involved in the aging brain. Neurobiol Aging 13:361–368
Borrás C, Sastre J, García-Sala D, Lloret A, Pallardó FV, Viña J (2003) Mitochondria from females exhibit higher antioxidant gene expression and lower oxidative damage than males. Free Radic Biol Med 34:546–552
Borras C, Gambini J, Vina J (2007) Mitochondrial oxidant generation is involved in determining why females live longer than males. Front Biosci 12:1008–1013
Bosetti F, Brizzi F, Barogi S, Mancuso M, Siciliano G, Tendi EA, Murri L, Rapoport SI, Solaini G (2002) Cytochrome c oxidase and mitochondrial F1F0-ATPase (ATP synthase) activities in platelets and brain from patients with Alzheimer’s disease. Neurobiol Aging 23:371–376
Cardoso SM, Proença MT, Santos S, Santana I, Oliveira CR (2004) Cytochrome c oxidase is decreased in Alzheimer’s disease platelets. Neurobiol Aging 25:105–110
Chandrasekaran K, Mehrabian Z, Spinnewyn B, Drieu K, Fiskum G (2001) Neuroprotective effects of bilobalide, a component of the Ginkgo biloba extract (EGb 761), in gerbil global brain ischemia. Brain Res 922:282–292
Chandrasekaran K, Mehrabian Z, Spinnewyn B, Chinopoulos C, Drieu K, Fiskum G (2003) Neuroprotective effects of bilobalide, a component of Ginkgo biloba extract (EGb 761) in global brain ischemia and in excitotoxicity-induced neuronal death. Pharmacopsychiatry 36(Suppl 1):S89–S94
Defeudis FV (2002) Bilobalide and neuroprotection. Pharmacol Res 46:565–568
Fukui H, Diaz F, Garcia S, Moraes CT (2007) Cytochrome c oxidase deficiency in neurons decreases both oxidative stress and amyloid formation in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci USA 104:14163–14168
Gagnon J, Kurowski TT, Wiesner RJ, Zak R (1991) Correlations between a nuclear and a mitochondrial mRNA of cytochrome c oxidase subunits, enzymatic activity and total mRNA content, in rat tissues. Mol Cell Biochem 107:21–29
Ghosh SS, Swerdlow RH, Miller SW, Sheeman B, Parker WD Jr, Davis RE (1999) Use of cytoplasmic hybrid cell lines for elucidating the role of mitochondrial dysfunction in Alzheimer’s disease and Parkinson’s disease. Ann N Y Acad Sci 893:176–191
Henderson VW, Buckwalter JG (1994) Cognitive deficits of men and women with Alzheimer disease. Neurology 44:90–96
Janssens D, Michiels C, Delaive E, Eliaers F, Drieu J, Remacle K (1995) Protection of hypoxia-induced ATP decrease in endothelial cells by Ginkgo biloba extract and bilobalide. Biochem Pharmacol 50:991–999
Janssens D, Remacle J, Drieu K, Michiels C (1999) Protection of mitochondrial respiration activity by bilobalide. Biochem Pharmacol 58:109–119
Kang D, Kim SH, Hamasaki N (2007) Mitochondrial transcription factor A (TFAM): roles in maintenance of mtDNA and cellular functions. Mitochondrion 7:39–44
Li LY, Zhao XL, Fei XF, Gu ZL, Qin ZH, Liang ZQ (2008) Bilobalide inhibits 6-OHDA-induced activation of NF-kappaB and loss of dopaminergic neurons in rat substantia nigra. Acta Pharmacol Sin 29:539–547
Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787–795
Mutisya EM, Bowling AC, Beal MF (1994) Cortical cytochrome oxidase activity is reduced in Alzheimer’s disease. J Neurochem 63:2179–2184
Parker WD Jr, Mahr NJ, Filley CM, Parks JK, Hughes D, Young DA, Cullum CM (1994) Reduced platelet cytochrome c oxidase activity in Alzheimer’s disease. Neurology 44:1086–1090
Richter C (1997) Reactive oxygen species and nitrogen species regulate mitochondrial Ca2+ homeostasis and respiration. Biosci Rep 17:53–66
Rodriguez-Gabriel MA, Burns G, McDonald WH, Martin V, Yates JR III, Bahler J, Russell P (2003) RNA-binding protein Csx1 mediates global control of gene expression in response to oxidative stress. EMBO J 22:6256–6266
Sato T, Teramoto T, Tanaka K, Ohnishi Y, Irifune M, Nishikawa T (2003) Effects of ovariectomy and calcium deficiency on learning and memory of eight-arm radial maze in middle-aged female rats. Behav Brain Res 142:207–216
Schwarze SR, Weindruch R, Aiken JM (1998) Oxidative stress and aging reduce COX I RNA and cytochrome oxidase activity in Drosophila. Free Radic Biol Med 25:740–747
Shi C, Xu J (2008) Increased vulnerability of brain to estrogen withdrawal-induced mitochondrial dysfunction with aging. J Bioenerg Biomembr 40:625–630
Shi C, Xu XW, Forster EL, Tang LF, Ge Z, Yew DT, Xu J (2008) Possible role of mitochondrial dysfunction in central neurodegeneration of ovariectomized rats. Cell Biochem Funct 26:172–178
Shi C, Fang L, Yew DT, Yao Z, Xu J (2010) Ginkgo biloba extract EGb761 protects against mitochondrial dysfunction in platelets and hippocampi in ovariectomized rats. Platelets 21:53–59
Sohal RS (1993) Aging, cytochrome oxidase activity, and hydrogen peroxide release by mitochondria. Free Radic Biol Med 14:583–588
Taanman JW (1997) Human cytochrome c oxidase, structure, function, and deficiency. J Bioenerg Biomembr 29:151–163
Viña J, Borrás C, Gambini J, Sastre J, Pallardó FV (2005) Why females live longer than males, control of longevity by sex hormones. Sci Aging Knowledge Environ 2005(23):pe17
Xu J, Zhu J, Shi C, Guo K, Yew DT (2007) Effects of genistein on hippocampal neurodegeneration of ovariectomized rats. J Mol Neurosci 31:101–112
Xu S, Zhou Z, Zhang L, Yu Z, Zhang W, Wang Y, Wang X, Li M, Chen Y, Chen C, He M, Zhang G, Zhong M (2010) Exposure to 1800 MHz radiofrequency radiation induces oxidative damage to mitochondrial DNA in primary cultured neurons. Brain Res 1311:189–196
Acknowledgment
Many thanks for support from the Guangdong Provincial Natural Science Foundation (No. 20090171110046) and Science Foundation of Ministry of Education of China (No. 9151008901000039).
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Chun Shi and Juntao Zou contribute to this work equally and are listed as co-first authors
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Shi, C., Zou, J., Li, G. et al. Bilobalide Protects Mitochondrial Function in Ovariectomized Rats by Up-regulation of mRNA and Protein Expression of Cytochrome c Oxidase Subunit I. J Mol Neurosci 45, 69–75 (2011). https://doi.org/10.1007/s12031-010-9388-z
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DOI: https://doi.org/10.1007/s12031-010-9388-z