Pinusolide and 15-methoxypinusolidic acid attenuate the neurotoxic effect of staurosporine in primary cultures of rat cortical cells

K. A. Koo, M. K. Lee, S. H. Kim, E. J. Jeong, S. Y. Kim, T. H. Oh, Y. C. Kim

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Background and purpose: Apoptosis is a fundamental process required for neuronal development but also occurs in most of the common neurodegenerative disorders. In an attempt to obtain an anti-apoptotic neuroprotective compound from natural products, we isolated the diterpenoids, pinusolide and 15-MPA, from B. orientalis and investigated their neuroprotective activity against staurosporine (STS) -induced neuronal apoptosis. In addition, we determined the anti-apoptotic mechanism of these compounds in rat cortical cells. Experimental approach: Primary cultures of rat cortical cells injured by STS were used as an in vitro assay system. Cells were pretreated with pinusolide or 15-MPA before exposure to STS. Anti-apoptotic activities were evaluated by the measurement of cytoplasmic condensation and nuclear fragmentation. The levels of cellular peroxide, malondialdehyde (MDA) and [Ca 2+ ] i , as well as the activities of superoxide dismutase (SOD) and caspase-3/7, were measured. Key results: Pinusolide and 15-MPA, at a concentration of 5.0 ìM, reduced the condensed nuclei and rise in [Ca 2+ ] i that accompanies apoptosis induced by 100 nM STS. Pinusolide and 15-MPA also protected the cellular activity of SOD, an antioxidative enzyme reduced by STS insult. Furthermore, the overproduction of reactive oxygen species and lipid peroxidation induced by STS was significantly reduced in pinusolide and 15-MPA treated cells. In addition, pinusolide and 15-MPA inhibited STS-induced caspase-3/7 activation. Conclusions and Implications: These results show that pinusolide and 15-MPA protect neuronal cells from STS-induced apoptosis, probably by preventing the increase in [Ca 2+ ] i and cellular oxidation caused by STS, and indicate that they could be used to treat neurodegenerative diseases.

Original languageEnglish
Pages (from-to)65-71
Number of pages7
JournalBritish Journal of Pharmacology
Volume150
Issue number1
DOIs
Publication statusPublished - 2007 Jan 27

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Staurosporine
Apoptosis
Caspase 7
Caspase 3
Neurodegenerative Diseases
Superoxide Dismutase
15-methoxypinusolidic acid
pinusolide
Diterpenes
Peroxides
Biological Products
Malondialdehyde
Lipid Peroxidation
Reactive Oxygen Species

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Koo, K. A. ; Lee, M. K. ; Kim, S. H. ; Jeong, E. J. ; Kim, S. Y. ; Oh, T. H. ; Kim, Y. C. / Pinusolide and 15-methoxypinusolidic acid attenuate the neurotoxic effect of staurosporine in primary cultures of rat cortical cells. In: British Journal of Pharmacology. 2007 ; Vol. 150, No. 1. pp. 65-71.
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abstract = "Background and purpose: Apoptosis is a fundamental process required for neuronal development but also occurs in most of the common neurodegenerative disorders. In an attempt to obtain an anti-apoptotic neuroprotective compound from natural products, we isolated the diterpenoids, pinusolide and 15-MPA, from B. orientalis and investigated their neuroprotective activity against staurosporine (STS) -induced neuronal apoptosis. In addition, we determined the anti-apoptotic mechanism of these compounds in rat cortical cells. Experimental approach: Primary cultures of rat cortical cells injured by STS were used as an in vitro assay system. Cells were pretreated with pinusolide or 15-MPA before exposure to STS. Anti-apoptotic activities were evaluated by the measurement of cytoplasmic condensation and nuclear fragmentation. The levels of cellular peroxide, malondialdehyde (MDA) and [Ca 2+ ] i , as well as the activities of superoxide dismutase (SOD) and caspase-3/7, were measured. Key results: Pinusolide and 15-MPA, at a concentration of 5.0 {\`i}M, reduced the condensed nuclei and rise in [Ca 2+ ] i that accompanies apoptosis induced by 100 nM STS. Pinusolide and 15-MPA also protected the cellular activity of SOD, an antioxidative enzyme reduced by STS insult. Furthermore, the overproduction of reactive oxygen species and lipid peroxidation induced by STS was significantly reduced in pinusolide and 15-MPA treated cells. In addition, pinusolide and 15-MPA inhibited STS-induced caspase-3/7 activation. Conclusions and Implications: These results show that pinusolide and 15-MPA protect neuronal cells from STS-induced apoptosis, probably by preventing the increase in [Ca 2+ ] i and cellular oxidation caused by STS, and indicate that they could be used to treat neurodegenerative diseases.",
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Pinusolide and 15-methoxypinusolidic acid attenuate the neurotoxic effect of staurosporine in primary cultures of rat cortical cells. / Koo, K. A.; Lee, M. K.; Kim, S. H.; Jeong, E. J.; Kim, S. Y.; Oh, T. H.; Kim, Y. C.

In: British Journal of Pharmacology, Vol. 150, No. 1, 27.01.2007, p. 65-71.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Pinusolide and 15-methoxypinusolidic acid attenuate the neurotoxic effect of staurosporine in primary cultures of rat cortical cells

AU - Koo, K. A.

AU - Lee, M. K.

AU - Kim, S. H.

AU - Jeong, E. J.

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AU - Kim, Y. C.

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N2 - Background and purpose: Apoptosis is a fundamental process required for neuronal development but also occurs in most of the common neurodegenerative disorders. In an attempt to obtain an anti-apoptotic neuroprotective compound from natural products, we isolated the diterpenoids, pinusolide and 15-MPA, from B. orientalis and investigated their neuroprotective activity against staurosporine (STS) -induced neuronal apoptosis. In addition, we determined the anti-apoptotic mechanism of these compounds in rat cortical cells. Experimental approach: Primary cultures of rat cortical cells injured by STS were used as an in vitro assay system. Cells were pretreated with pinusolide or 15-MPA before exposure to STS. Anti-apoptotic activities were evaluated by the measurement of cytoplasmic condensation and nuclear fragmentation. The levels of cellular peroxide, malondialdehyde (MDA) and [Ca 2+ ] i , as well as the activities of superoxide dismutase (SOD) and caspase-3/7, were measured. Key results: Pinusolide and 15-MPA, at a concentration of 5.0 ìM, reduced the condensed nuclei and rise in [Ca 2+ ] i that accompanies apoptosis induced by 100 nM STS. Pinusolide and 15-MPA also protected the cellular activity of SOD, an antioxidative enzyme reduced by STS insult. Furthermore, the overproduction of reactive oxygen species and lipid peroxidation induced by STS was significantly reduced in pinusolide and 15-MPA treated cells. In addition, pinusolide and 15-MPA inhibited STS-induced caspase-3/7 activation. Conclusions and Implications: These results show that pinusolide and 15-MPA protect neuronal cells from STS-induced apoptosis, probably by preventing the increase in [Ca 2+ ] i and cellular oxidation caused by STS, and indicate that they could be used to treat neurodegenerative diseases.

AB - Background and purpose: Apoptosis is a fundamental process required for neuronal development but also occurs in most of the common neurodegenerative disorders. In an attempt to obtain an anti-apoptotic neuroprotective compound from natural products, we isolated the diterpenoids, pinusolide and 15-MPA, from B. orientalis and investigated their neuroprotective activity against staurosporine (STS) -induced neuronal apoptosis. In addition, we determined the anti-apoptotic mechanism of these compounds in rat cortical cells. Experimental approach: Primary cultures of rat cortical cells injured by STS were used as an in vitro assay system. Cells were pretreated with pinusolide or 15-MPA before exposure to STS. Anti-apoptotic activities were evaluated by the measurement of cytoplasmic condensation and nuclear fragmentation. The levels of cellular peroxide, malondialdehyde (MDA) and [Ca 2+ ] i , as well as the activities of superoxide dismutase (SOD) and caspase-3/7, were measured. Key results: Pinusolide and 15-MPA, at a concentration of 5.0 ìM, reduced the condensed nuclei and rise in [Ca 2+ ] i that accompanies apoptosis induced by 100 nM STS. Pinusolide and 15-MPA also protected the cellular activity of SOD, an antioxidative enzyme reduced by STS insult. Furthermore, the overproduction of reactive oxygen species and lipid peroxidation induced by STS was significantly reduced in pinusolide and 15-MPA treated cells. In addition, pinusolide and 15-MPA inhibited STS-induced caspase-3/7 activation. Conclusions and Implications: These results show that pinusolide and 15-MPA protect neuronal cells from STS-induced apoptosis, probably by preventing the increase in [Ca 2+ ] i and cellular oxidation caused by STS, and indicate that they could be used to treat neurodegenerative diseases.

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