Silibinin Protects Against Isoproterenol-Induced Rat Cardiac Myocyte Injury Through Mitochondrial Pathway After Up-regulation of SIRT1
Terminally differentiated adult injured cardiac myocytes have been used for various animal models of heart failure. It has recently been shown that isoproterenol induces injury in rat neonatal cardiac myocytes via a β-adrenergic pathway, suggesting that it might be one of the factors involved in myo...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2006-01-01
|
| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319343518 |
| _version_ | 1811199399412367360 |
|---|---|
| author | Bei Zhou Li-Jun Wu Lin-Hao Li Shin-ichi Tashiro Satoshi Onodera Fumiaki Uchiumi Takashi Ikejima |
| author_facet | Bei Zhou Li-Jun Wu Lin-Hao Li Shin-ichi Tashiro Satoshi Onodera Fumiaki Uchiumi Takashi Ikejima |
| author_sort | Bei Zhou |
| collection | DOAJ |
| description | Terminally differentiated adult injured cardiac myocytes have been used for various animal models of heart failure. It has recently been shown that isoproterenol induces injury in rat neonatal cardiac myocytes via a β-adrenergic pathway, suggesting that it might be one of the factors involved in myocardial cell injury in heart failure in vivo. In the study, silibinin, a plant flavanoid from milk thistle was first evaluated for its protective effect against β-adrenergic agonist isoproterenol-induced injury in cultured rat neonatal cardiac myocytes. The viability, activation of lactate dehydrogenase (LDH), and content of maleic dialdehyde (MDA) were chosen for measuring the degree of cardiac myocytes injury. As a result, silibinin protected isoproterenol-treated rat cardiac myocytes from death and significantly decreased LDH release and MDA production. Silibinin increased superoxide dismutase activity, decreased [Ca2+]i, and increased mitochondrial membrane potential (∆Ψ). Furthermore, the release of pro-apoptotic cytochrome c from mitochondria was reduced by silibinin. Silibinin increased the expression of anti-apoptotic Bcl-2 family protein Bcl-2, and up-regulation of SIRT1 inhibited the translocation of Bax from cytoplasm to mitochondria, which caused mitochondrial dysfunction and cell injury. These results demonstrate that silibinin protects against isoproterenol-induced cardiac myocytes injury through resuming mitochondrial function and regulating the expression of SIRT1 and Bcl-2 family members. Keywords:: silibinin, cardiac myocyte (rat), injury, mitochondrial membrane potential, SIRT1 |
| first_indexed | 2024-04-12T01:47:40Z |
| format | Article |
| id | doaj.art-e99da10e20b944e0867b575d160870a2 |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-04-12T01:47:40Z |
| publishDate | 2006-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-e99da10e20b944e0867b575d160870a22022-12-22T03:53:01ZengElsevierJournal of Pharmacological Sciences1347-86132006-01-011024387395Silibinin Protects Against Isoproterenol-Induced Rat Cardiac Myocyte Injury Through Mitochondrial Pathway After Up-regulation of SIRT1Bei Zhou0Li-Jun Wu1Lin-Hao Li2Shin-ichi Tashiro3Satoshi Onodera4Fumiaki Uchiumi5Takashi Ikejima6China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Phytochemistry, Shenyang Pharmaceutical University, Shenyang 110016, ChinaChina-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, ChinaDepartment of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo 194-8543, JapanDepartment of Clinical and Biomedical Sciences, Showa Pharmaceutical University, Tokyo 194-8543, JapanDepartment of Gene Regulation, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, JapanChina-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016, China; Corresponding author. ikejimat@vip.sina.comTerminally differentiated adult injured cardiac myocytes have been used for various animal models of heart failure. It has recently been shown that isoproterenol induces injury in rat neonatal cardiac myocytes via a β-adrenergic pathway, suggesting that it might be one of the factors involved in myocardial cell injury in heart failure in vivo. In the study, silibinin, a plant flavanoid from milk thistle was first evaluated for its protective effect against β-adrenergic agonist isoproterenol-induced injury in cultured rat neonatal cardiac myocytes. The viability, activation of lactate dehydrogenase (LDH), and content of maleic dialdehyde (MDA) were chosen for measuring the degree of cardiac myocytes injury. As a result, silibinin protected isoproterenol-treated rat cardiac myocytes from death and significantly decreased LDH release and MDA production. Silibinin increased superoxide dismutase activity, decreased [Ca2+]i, and increased mitochondrial membrane potential (∆Ψ). Furthermore, the release of pro-apoptotic cytochrome c from mitochondria was reduced by silibinin. Silibinin increased the expression of anti-apoptotic Bcl-2 family protein Bcl-2, and up-regulation of SIRT1 inhibited the translocation of Bax from cytoplasm to mitochondria, which caused mitochondrial dysfunction and cell injury. These results demonstrate that silibinin protects against isoproterenol-induced cardiac myocytes injury through resuming mitochondrial function and regulating the expression of SIRT1 and Bcl-2 family members. Keywords:: silibinin, cardiac myocyte (rat), injury, mitochondrial membrane potential, SIRT1http://www.sciencedirect.com/science/article/pii/S1347861319343518 |
| spellingShingle | Bei Zhou Li-Jun Wu Lin-Hao Li Shin-ichi Tashiro Satoshi Onodera Fumiaki Uchiumi Takashi Ikejima Silibinin Protects Against Isoproterenol-Induced Rat Cardiac Myocyte Injury Through Mitochondrial Pathway After Up-regulation of SIRT1 Journal of Pharmacological Sciences |
| title | Silibinin Protects Against Isoproterenol-Induced Rat Cardiac Myocyte Injury Through Mitochondrial Pathway After Up-regulation of SIRT1 |
| title_full | Silibinin Protects Against Isoproterenol-Induced Rat Cardiac Myocyte Injury Through Mitochondrial Pathway After Up-regulation of SIRT1 |
| title_fullStr | Silibinin Protects Against Isoproterenol-Induced Rat Cardiac Myocyte Injury Through Mitochondrial Pathway After Up-regulation of SIRT1 |
| title_full_unstemmed | Silibinin Protects Against Isoproterenol-Induced Rat Cardiac Myocyte Injury Through Mitochondrial Pathway After Up-regulation of SIRT1 |
| title_short | Silibinin Protects Against Isoproterenol-Induced Rat Cardiac Myocyte Injury Through Mitochondrial Pathway After Up-regulation of SIRT1 |
| title_sort | silibinin protects against isoproterenol induced rat cardiac myocyte injury through mitochondrial pathway after up regulation of sirt1 |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319343518 |
| work_keys_str_mv | AT beizhou silibininprotectsagainstisoproterenolinducedratcardiacmyocyteinjurythroughmitochondrialpathwayafterupregulationofsirt1 AT lijunwu silibininprotectsagainstisoproterenolinducedratcardiacmyocyteinjurythroughmitochondrialpathwayafterupregulationofsirt1 AT linhaoli silibininprotectsagainstisoproterenolinducedratcardiacmyocyteinjurythroughmitochondrialpathwayafterupregulationofsirt1 AT shinichitashiro silibininprotectsagainstisoproterenolinducedratcardiacmyocyteinjurythroughmitochondrialpathwayafterupregulationofsirt1 AT satoshionodera silibininprotectsagainstisoproterenolinducedratcardiacmyocyteinjurythroughmitochondrialpathwayafterupregulationofsirt1 AT fumiakiuchiumi silibininprotectsagainstisoproterenolinducedratcardiacmyocyteinjurythroughmitochondrialpathwayafterupregulationofsirt1 AT takashiikejima silibininprotectsagainstisoproterenolinducedratcardiacmyocyteinjurythroughmitochondrialpathwayafterupregulationofsirt1 |