title: Involvement of heme oxygenase-1 in neuroprotection by sanguinarine against glutamate-triggered apoptosis in HT22 neuronal cells.
abstract: Sanguinarine is a natural compound isolated from the roots of Macleaya cordata and M. microcarpa, has been reported to possess several biological activities such as anti-inflammatory and anti-oxidant effects. In the present study, we demonstrated that sanguinarine markedly induces the expression of HO-1 which leads to a neuroprotective response in mouse hippocampus-derived neuronal HT22 cells from apoptotic cell death induced by glutamate. Sanguinarine significantly attenuated the loss of mitochondrial function and membrane integrity associated with glutamate-induced neurotoxicity. Sanguinarine protected against glutamate-induced neurotoxicity through inhibition of HT22 cell apoptosis. JC-1 staining, which is a well-established measure of mitochondrial damage, was decreased after treatment with sanguinarine in glutamate-challenged HT22cells. In addition, sanguinarine diminished the intracellular accumulation of ROS and Ca(2+). Sanguinarine also induced HO-1, NQO-1 expression via activation of Nrf2. Additionally, we found that si RNA mediated knock-down of Nrf2 or HO-1 significantly inhibited sanguinarine-induced neuroprotective response. These findings revealed the therapeutic potential of sanguinarine in preventing the neurodegenerative diseases.
authors.affiliation: Bio-IT Fusion Technology Research Institute, Pusan National University, Busan, Republic of Korea; Research Center for Anti-Aging Technology Development, Pusan National University, Busan, Republic of Korea.
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Park
authors.affiliation: Department of Microbiology, Pusan National University, Busan, Republic of Korea; Research Center for Anti-Aging Technology Development, Pusan National University, Busan, Republic of Korea.
authors.forename: Mei Ling
authors.initials: ML
authors.lastname: Jin
authors.affiliation: Bio-IT Fusion Technology Research Institute, Pusan National University, Busan, Republic of Korea; Research Center for Anti-Aging Technology Development, Pusan National University, Busan, Republic of Korea.
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Center for Biomedical Informatics, College of Medicine, Pusan National University, Busan, Republic of Korea; Research Center for Anti-Aging Technology Development, Pusan National University, Busan, Republic of Korea.
authors.forename: Cheol-Min
authors.initials: CM
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Pusan National University, Busan, Republic of Korea; Research Center for Anti-Aging Technology Development, Pusan National University, Busan, Republic of Korea.
authors.forename: Sang Joon
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Bio-IT Fusion Technology Research Institute, Pusan National University, Busan, Republic of Korea; Research Center for Anti-Aging Technology Development, Pusan National University, Busan, Republic of Korea; Department of Nanomaterials Engineering, Pusan National University, Busan, Republic of Korea. Electronic address: gtpark@pusan.ac.kr.
authors.forename: Geuntae
authors.initials: G
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D053119:Benzophenanthridines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D018698:Glutamic Acid / Q000009:adverse effects*; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D007546:Isoquinolines / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D051336:Mitochondrial Membranes / Q000187:drug effects; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D053119:Benzophenanthridines; D007546:Isoquinolines; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; C005705:sanguinarine; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D016660:NAD(P)H Dehydrogenase (Quinone); C491732:Nqo1 protein, mouse; D002118:Calcium
keywords: Glutamate; Heme oxygenase-1; Neuroprotection; Sanguinarine