Abstract
Polyphenols are known to exhibit wide spectrum of benefit for brain health and to protect from several neurodegenerative diseases. The present study was sought to determine the neuroprotective effects of Rosmarinus officinalis’ polyphenols (luteolin, carnosic acid, and rosmarinic acid) through the investigation of stress-related proteins. We carried out measurement of the expression of heat-shock protein (Hsp) 47 promoter in heat stressed Chinese hamster ovary transfected cells. We performed proteomic analysis and confirmed gene expression by real time PCR in PC12 cells. Results showed that these compounds modulated significant and different effects on the expression of 4 stress-related proteins: heat shock protein 90 α (Hsp90), Transitional endoplasmic reticulum ATPase (VCP/p97), Nucleoside diphosphate kinase (NDK), and Hypoxia up-regulated protein 1 (HYOU1)) at translational and post translational levels in PC12 cells and they downregulated the expression of Hsp47 activity in Chinese hamster transformed cells. These findings suggest that luteolin, carnosic acid, and rosmarinic acid may modulate the neuroprotective defense system against cellular stress insults and increase neuro-thermotolerance.
Similar content being viewed by others
References
Ali YO, Kitay BM, Zhai RG (2010) Dealing with misfolded proteins: examining the neuroprotective role of molecular chaperones in neurodegeneration. Molecules 15:6859–6887
Chen S, Brown IR (2007) Neuronal expression of constitutive heat shock proteins: implications for neurodegenerative diseases. Cell Stress Chaperones 12:51–58
Dwyer DS, Liu Y, Miao S, Bradley RJ (1996) Neuronal differentiation in PC12 cells is accompanied by diminished inducibility of Hsp70 and Hsp 60 in response to heat and ethanol. Neurochem Res 21:659–666
El Omri A, Han J, Yamada P, Kawada K, Abdrabbah MB, Isoda H (2010) Rosmarinus officinalis polyphenols activate cholinergic activities in PC12 cells through phosphorylation of ERK1/2. J Ethnopharmacol 131:451–458
Halliwell B (2008) Are polyphenols antioxidants or pro-oxidants? What do we learn from cell culture and in vivo studies? Arch Biochem Biophys 476:107–112
Han J, Miyamae Y, Shigemori H, Isoda H (2010) Neuroprotective effect of 3,5-di-Ocaffeoylquinic acid on SH-SY5Y cells and senescence-accelerated-prone mice 8 through the up-regulation of phosphoglycerate kinase-1. Neuroscience 169:1039–1045
Isoda H, Koyama T, Tasaki M, Oka S, Sugiura N, Maekawa T, Inamori Y, Yokota S, Kitahara M, Nagata K (2004) High-sensitive detection of environmental pollutants. US Patent 6740521 B2
Kim SH, Fountoulakis M, Cairns NJ, Lubec G (2002) Human brain nucleoside diphosphate kinase activity is decreased in Alzheimer’s disease and Down syndrome. Biochem Biophys Res Commun 296:970–975
Kimura N, Shimada N, Ishijima Y, Fukuda M, Takagi Y, Ishikawa N (2003) Nucleoside diphosphate kinases in mammalian signal transduction systems: recent development and perspective. J Bioenerg Biomembr 35:41–47
Kobayashi T, Tanaka K, Inoue K, Kakizuka A (2002) Functional ATPase activity of p97/valosin-containing protein (VCP) is required for the quality control of endoplasmic reticulum in neuronally differentiated mammalian PC12 cells. J Biol Chem 277:47358–47365
Kosaka K, Mimura J, Itoh K, Satoh T, Shimojo Y, Kitajima C, Maruyama A, Yamamoto M, Shirasawa T (2010) Role of Nrf2 and p62/ZIP in the neurite outgrowth by carnosic acid in PC12h cells. J Biochem 147:73–81
Lin CW, Wu MJ, Liu IY, Su JD, Yen JH (2010) Neurotrophic and cytoprotective action of luteolin in PC12 cells through ERK-dependent induction of Nrf2-driven HO-1 expression. J Agric Food Chem 58:4477–4486
Liu R, Gao M, Qiang GF, Zhang TT, Lan X, Ying J, Du GH (2009) The anti-amnesic effect of luteolin against amyloid β25–35 peptide induced toxicity in mice involve the protection of the neurovascular unit. Neuroscience 162:1232–1243
Luo W, Dou F, Rodina A, Chip S, Kim J, Zhao Q, Moulick K, Aguirre J, Wu N, Greengard P, Chiosis G (2007) Roles of heat-shock protein 90 in maintaining and facilitating the neurodegenerative phenotype in tauopathies. Proc Natl Acad Sci USA. 104:9511–9516
Luo W, Sun W, Taldone T, Rodina A, Chiosis G (2010) Heat shock protein 90 in neurodegenerative diseases. Mol Neurodegener 5:24
Nagahama M, Suzuki M, Hamada Y, Hatsuzawa K, Tani K, Yamamoto A, Tagaya M (2003) SVIP is a novel VCP/p97-interacting protein whose expression causes cell vacuolation. Mol Biol Cell 14:262–273
Ortega RM (2006) Importance of functional foods in the Mediterranean diet. Public Health Nutr 9:1136–1140
Oza J, Yang J, Chen KY, Liu AY (2008) Changes in the regulation of heat shock gene expression in neuronal cell differentiation. Cell Stress Chaperones 13:73–84
Ozacmak VH, Barut F, Ozacmak HS (2009) Melatonin provides neuroprotection by reducing oxidative stress and HSP70 expression during chronic cerebral hypoperfusion in ovariectomized rats. J Pineal Res 47:156–163
Park SE, Kim S, Sapkota K, Kim SJ (2010) Neuroprotective effect of Rosmarinus officinalis extract on Human dopaminergic cell line, SH-SY5Y. Cell Mol Neurobiol 30:759–767
Putics A, Végh EM, Csermely P, Soti C (2008) Resveratrol induces the heat-shock response and protects human cells from severe heat stress. Antioxid Redox Signal 10:65–75
Queen BL, Tollefsbol TO (2010) Polyphenols and aging. Curr Aging Sci 3:34–42
Rajeswari A, Sabesan M (2008) Inhibition of monoamine oxidase-B by the polyphenolic compound, curcumin and its metabolite tetrahydrocurcumin, in a model of Parkinson’s disease induced by MPTP neurodegeneration in mice. Inflammopharmacol 16:96–99
Ramassamy C (2006) Emerging role of polyphenolic compounds in the treatment of neurodegenerative diseases: a review of their intracellular targets. Eur J Pharmacol 545:51–64
Rocnik EF, van der Veer E, Cao H, Hegele RA, Pickering JG (2002) Functional linkage between the endoplasmic reticulum protein Hsp47 and procollagen expression in human vascular smooth muscle cells. J Biol Chem 277:38571–38578
Samali A, Fitzgerald U, Deegan S, Gupta S (2010) Methods for monitoring endoplasmic reticulum stress and the unfolded protein response. Int J Cell Biol. doi:10.1155/2010/830307
Shimojo Y, Kosaka K, Noda Y, Shimizu T, Shirasawa T (2010) Effect of rosmarinic acid in motor dysfunction and life span in a mouse model of familial amyotrophic lateral sclerosis. J Neurosci Res 88:896–904
Spencer JPE (2009) Flavonoids and brain health: multiple effects underpinned by common mechanisms. Genes Nutr 4:243–250
Sun AY, Wang Q, Simonyi A, Sun GY (2010) Resveratrol as a therapeutic agent for neurodegenerative diseases. Mol Neurobiol 41:375–383
Taguchi T, Razzaque MS (2007) The collagen-specific molecular chaperone Hsp47: is there a role in fibrosis? Trends Mol Med 13:45–53
Wilson MA, Shukitt-Hale B, Kalt W, Ingram DK, Joseph JA, Wolkow CA (2006) Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell 5:59–68
Winklhofer KF, Tatzelt J, Haass C (2008) The two faces of protein misfolding: gain- and loss-of-function in neurodegenerative diseases. EMBO J 27:336–349
Yang W, Liu P, Liu Y, Wang Q, Tong Y, Ji J (2006) Proteomic analysis of rat pheochromocytoma PC12 cells. Proteomics 6:2982–2990
Yano M, Mori S, Kido H (1999) Intrinsic nucleoside diphosphate kinase-like activity is a novel function of the 20 S proteasome. J Biol Chem 274:34375–34382
Zhao L, Rosales C, Seburn K, Ron D, Ackerman SL (2010) Alteration of the unfolded protein response modifies neurodegeneration in a mouse model of Marinesco-Sjögren syndrome. Hum Mol Genet 19:25–35
Acknowledgments
This work was partially supported by by Mitsui & Co., Ltd. Environment Fund.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
E. L. Omri, A., Han, J., Ben Abdrabbah, M. et al. Down regulation effect of Rosmarinus officinalis polyphenols on cellular stress proteins in rat pheochromocytoma PC12 cells. Cytotechnology 64, 231–240 (2012). https://doi.org/10.1007/s10616-011-9352-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10616-011-9352-y