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Erschienen in: Metabolic Brain Disease 1/2015

01.02.2015 | Research Article

Berberine protects homocysteic acid-induced HT-22 cell death: involvement of Akt pathway

verfasst von: Meihui Chen, Min Tan, Minghua Jing, Anmin Liu, Qinyu Liu, Shijun Wen, Ziwei Chen, Xiaojuan Chao, Xixin He, Charles Ramassamy, Youheng Gao, Rongbiao Pi

Erschienen in: Metabolic Brain Disease | Ausgabe 1/2015

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Abstract

Berberine (BBR), one of the major constituents of Chinese herb Rhizoma coptidis, has been reported to exert beneficial effects to various diseases, including Alzheimer’s disease (AD). In the present work, we aimed to investigate the effects of BBR on neuronal cell death induced by homocysteic acid (HCA), which was considered as a risk of AD. BBR significantly reduced HCA-induced reactive oxygen species (ROS) generation, lactate dehydrogenase release and subsequent cell death. LY294002, the PI3K inhibitor, blocked the protection as well as the up-regulation of Akt phosphorylation of BBR. Taken together, our results indicate that BBR protects HCA-induced HT-22 cell death partly via modulating Akt pathway, suggesting BBR may be a promising therapeutic agent for the treatment of HCA-related diseases, including AD.
Literatur
Zurück zum Zitat Bae J, Lee D, Kim YK, Gil M, Lee JY, Lee KJ (2013) Berberine protects 6-hydroxydopamine-induced human dopaminergic neuronal cell death through the induction of heme oxygenase-1. Mol Cells 35:151–157PubMedCentralPubMedCrossRef Bae J, Lee D, Kim YK, Gil M, Lee JY, Lee KJ (2013) Berberine protects 6-hydroxydopamine-induced human dopaminergic neuronal cell death through the induction of heme oxygenase-1. Mol Cells 35:151–157PubMedCentralPubMedCrossRef
Zurück zum Zitat Brunet A, Datta SR, Greenberg ME (2001) Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol 11:297–305PubMedCrossRef Brunet A, Datta SR, Greenberg ME (2001) Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol 11:297–305PubMedCrossRef
Zurück zum Zitat Davis JB, Maher P (1994) Protein kinase C activation inhibits glutamate-induced cytotoxicity in a neuronal cell line. Brain Res 652:169–173PubMedCrossRef Davis JB, Maher P (1994) Protein kinase C activation inhibits glutamate-induced cytotoxicity in a neuronal cell line. Brain Res 652:169–173PubMedCrossRef
Zurück zum Zitat Folbergrova J, Jesina P, Drahota Z, Lisy V, Haugvicova R, Vojtiskova A, Houstek J (2007) Mitochondrial complex I inhibition in cerebral cortex of immature rats following homocysteic acid-induced seizures. Exp Neurol 204:597–609PubMedCrossRef Folbergrova J, Jesina P, Drahota Z, Lisy V, Haugvicova R, Vojtiskova A, Houstek J (2007) Mitochondrial complex I inhibition in cerebral cortex of immature rats following homocysteic acid-induced seizures. Exp Neurol 204:597–609PubMedCrossRef
Zurück zum Zitat Hasegawa T, Ukai W, Jo DG, Xu X, Mattson MP, Nakagawa M, Araki W, Saito T, Yamada T (2005) Homocysteic acid induces intraneuronal accumulation of neurotoxic Abeta42: implications for the pathogenesis of Alzheimer’s disease. J Neurosci Res 80:869–876PubMedCrossRef Hasegawa T, Ukai W, Jo DG, Xu X, Mattson MP, Nakagawa M, Araki W, Saito T, Yamada T (2005) Homocysteic acid induces intraneuronal accumulation of neurotoxic Abeta42: implications for the pathogenesis of Alzheimer’s disease. J Neurosci Res 80:869–876PubMedCrossRef
Zurück zum Zitat Hasegawa T, Mikoda N, Kitazawa M, Laferla FM (2010) Treatment of Alzheimer’s disease with anti-homocysteic acid antibody in 3xTg-AD male mice. PLoS One 5:e8593PubMedCentralPubMedCrossRef Hasegawa T, Mikoda N, Kitazawa M, Laferla FM (2010) Treatment of Alzheimer’s disease with anti-homocysteic acid antibody in 3xTg-AD male mice. PLoS One 5:e8593PubMedCentralPubMedCrossRef
Zurück zum Zitat Hsu YY, Chen CS, Wu SN, Jong YJ, Lo YC (2012) Berberine activates Nrf2 nuclear translocation and protects against oxidative damage via a phosphatidylinositol 3-kinase/Akt-dependent mechanism in NSC34 motor neuron-like cells. Eur J Pharm Sci 46:415–425PubMedCrossRef Hsu YY, Chen CS, Wu SN, Jong YJ, Lo YC (2012) Berberine activates Nrf2 nuclear translocation and protects against oxidative damage via a phosphatidylinositol 3-kinase/Akt-dependent mechanism in NSC34 motor neuron-like cells. Eur J Pharm Sci 46:415–425PubMedCrossRef
Zurück zum Zitat Ikonomidou C, Qin Qin Y, Labruyere J, Olney JW (1996) Motor neuron degeneration induced by excitotoxin agonists has features in common with those seen in the SOD-1 transgenic mouse model of amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 55:211–224PubMedCrossRef Ikonomidou C, Qin Qin Y, Labruyere J, Olney JW (1996) Motor neuron degeneration induced by excitotoxin agonists has features in common with those seen in the SOD-1 transgenic mouse model of amyotrophic lateral sclerosis. J Neuropathol Exp Neurol 55:211–224PubMedCrossRef
Zurück zum Zitat Jung SH, Kim BJ, Lee EH, Osborne NN (2010) Isoquercitrin is the most effective antioxidant in the plant Thuja orientalis and able to counteract oxidative-induced damage to a transformed cell line (RGC-5 cells). Neurochem Int 57:713–721PubMedCrossRef Jung SH, Kim BJ, Lee EH, Osborne NN (2010) Isoquercitrin is the most effective antioxidant in the plant Thuja orientalis and able to counteract oxidative-induced damage to a transformed cell line (RGC-5 cells). Neurochem Int 57:713–721PubMedCrossRef
Zurück zum Zitat Kulkarni SK, Dhir A (2010) Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders. Phytother Res 24:317–324PubMedCrossRef Kulkarni SK, Dhir A (2010) Berberine: a plant alkaloid with therapeutic potential for central nervous system disorders. Phytother Res 24:317–324PubMedCrossRef
Zurück zum Zitat Markesbery WR, Carney JM (1999) Oxidative alterations in Alzheimer’s disease. Brain Pathol 9:133–146PubMedCrossRef Markesbery WR, Carney JM (1999) Oxidative alterations in Alzheimer’s disease. Brain Pathol 9:133–146PubMedCrossRef
Zurück zum Zitat Obeid R, Herrmann W (2006) Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett 580:2994–3005PubMedCrossRef Obeid R, Herrmann W (2006) Mechanisms of homocysteine neurotoxicity in neurodegenerative diseases with special reference to dementia. FEBS Lett 580:2994–3005PubMedCrossRef
Zurück zum Zitat Ratan RR, Murphy TH, Baraban JM (1994) Macromolecular synthesis inhibitors prevent oxidative stress-induced apoptosis in embryonic cortical neurons by shunting cysteine from protein synthesis to glutathione. J Neurosci 14:4385–4392PubMed Ratan RR, Murphy TH, Baraban JM (1994) Macromolecular synthesis inhibitors prevent oxidative stress-induced apoptosis in embryonic cortical neurons by shunting cysteine from protein synthesis to glutathione. J Neurosci 14:4385–4392PubMed
Zurück zum Zitat Ryder J, Su Y, Ni B (2004) Akt/GSK3beta serine/threonine kinases: evidence for a signalling pathway mediated by familial Alzheimer’s disease mutations. Cell Signal 16:187–200PubMedCrossRef Ryder J, Su Y, Ni B (2004) Akt/GSK3beta serine/threonine kinases: evidence for a signalling pathway mediated by familial Alzheimer’s disease mutations. Cell Signal 16:187–200PubMedCrossRef
Zurück zum Zitat Shu Y, Zhang H, Kang T, Zhang JJ, Yang Y, Liu H, Zhang L (2013) PI3K/Akt signal pathway involved in the cognitive impairment caused by chronic cerebral hypoperfusion in rats. PLoS One 8:e81901PubMedCentralPubMedCrossRef Shu Y, Zhang H, Kang T, Zhang JJ, Yang Y, Liu H, Zhang L (2013) PI3K/Akt signal pathway involved in the cognitive impairment caused by chronic cerebral hypoperfusion in rats. PLoS One 8:e81901PubMedCentralPubMedCrossRef
Zurück zum Zitat Sompol P, Ittarat W, Tangpong J, Chen Y, Doubinskaia I, Batinic-Haberle I, Abdul HM, Butterfield DA, St Clair DK (2008) A neuronal model of Alzheimer’s disease: an insight into the mechanisms of oxidative stress-mediated mitochondrial injury. Neuroscience 153:120–130PubMedCentralPubMedCrossRef Sompol P, Ittarat W, Tangpong J, Chen Y, Doubinskaia I, Batinic-Haberle I, Abdul HM, Butterfield DA, St Clair DK (2008) A neuronal model of Alzheimer’s disease: an insight into the mechanisms of oxidative stress-mediated mitochondrial injury. Neuroscience 153:120–130PubMedCentralPubMedCrossRef
Zurück zum Zitat Stein TD, Johnson JA (2002) Lack of neurodegeneration in transgenic mice overexpressing mutant amyloid precursor protein is associated with increased levels of transthyretin and the activation of cell survival pathways. J Neurosci 22:7380–7388PubMed Stein TD, Johnson JA (2002) Lack of neurodegeneration in transgenic mice overexpressing mutant amyloid precursor protein is associated with increased levels of transthyretin and the activation of cell survival pathways. J Neurosci 22:7380–7388PubMed
Zurück zum Zitat Tan M, Ouyang Y, Jin M, Chen M, Liu P, Chao X, Chen Z, Chen X, Ramassamy C, Gao Y, Pi R (2013) Downregulation of Nrf2/HO-1 pathway and activation of JNK/c-Jun pathway are involved in homocysteic acid-induced cytotoxicity in HT-22 cells. Toxicol Lett 223(1):1–8PubMedCrossRef Tan M, Ouyang Y, Jin M, Chen M, Liu P, Chao X, Chen Z, Chen X, Ramassamy C, Gao Y, Pi R (2013) Downregulation of Nrf2/HO-1 pathway and activation of JNK/c-Jun pathway are involved in homocysteic acid-induced cytotoxicity in HT-22 cells. Toxicol Lett 223(1):1–8PubMedCrossRef
Zurück zum Zitat Wang L, Ankati H, Akubathini SK, Balderamos M, Storey CA, Patel AV, Price V, Kretzschmar D, Biehl ER, D’mello SR (2010) Identification of novel 1,4-benzoxazine compounds that are protective in tissue culture and in vivo models of neurodegeneration. J Neurosci Res 88:1970–1984PubMed Wang L, Ankati H, Akubathini SK, Balderamos M, Storey CA, Patel AV, Price V, Kretzschmar D, Biehl ER, D’mello SR (2010) Identification of novel 1,4-benzoxazine compounds that are protective in tissue culture and in vivo models of neurodegeneration. J Neurosci Res 88:1970–1984PubMed
Zurück zum Zitat Wei W, Wang X, Kusiak JW (2002) Signaling events in amyloid beta-peptide-induced neuronal death and insulin-like growth factor I protection. J Biol Chem 277:17649–17656PubMedCrossRef Wei W, Wang X, Kusiak JW (2002) Signaling events in amyloid beta-peptide-induced neuronal death and insulin-like growth factor I protection. J Biol Chem 277:17649–17656PubMedCrossRef
Metadaten
Titel
Berberine protects homocysteic acid-induced HT-22 cell death: involvement of Akt pathway
verfasst von
Meihui Chen
Min Tan
Minghua Jing
Anmin Liu
Qinyu Liu
Shijun Wen
Ziwei Chen
Xiaojuan Chao
Xixin He
Charles Ramassamy
Youheng Gao
Rongbiao Pi
Publikationsdatum
01.02.2015
Verlag
Springer US
Erschienen in
Metabolic Brain Disease / Ausgabe 1/2015
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI
https://doi.org/10.1007/s11011-014-9580-x

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