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Structure‐Function Relationships of Microcystins, Liver Tumor Promoters, in Interaction with Protein Phosphatase

Microcystins, isolated from toxic blue‐green algae, are potent inhibitors of protein phosphatases 1 and 2A. Recently, we have reported that mierocystin LR has a potent tumor‐promoting activity on rat liver initiated with diethylnitrosamine. The structure of microcystins is unique in having an unusua...

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Autores principales: Nishiwaki‐Matsushima, Rie, Nishiwaki, Shinji, Ohta, Tetsuya, Yoshizawa, Seiji, Suganuma, Masami, Harada, Ken‐ichi, Watanabe, Mariyo F., Fujiki, Hirota
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Blackwell Publishing Ltd 1991
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918597/
https://www.ncbi.nlm.nih.gov/pubmed/1657848
http://dx.doi.org/10.1111/j.1349-7006.1991.tb01933.x
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author Nishiwaki‐Matsushima, Rie
Nishiwaki, Shinji
Ohta, Tetsuya
Yoshizawa, Seiji
Suganuma, Masami
Harada, Ken‐ichi
Watanabe, Mariyo F.
Fujiki, Hirota
author_facet Nishiwaki‐Matsushima, Rie
Nishiwaki, Shinji
Ohta, Tetsuya
Yoshizawa, Seiji
Suganuma, Masami
Harada, Ken‐ichi
Watanabe, Mariyo F.
Fujiki, Hirota
author_sort Nishiwaki‐Matsushima, Rie
collection PubMed
description Microcystins, isolated from toxic blue‐green algae, are potent inhibitors of protein phosphatases 1 and 2A. Recently, we have reported that mierocystin LR has a potent tumor‐promoting activity on rat liver initiated with diethylnitrosamine. The structure of microcystins is unique in having an unusual ammo acid, 3‐amino‐9‐methoxy‐10‐phenyl‐2,6,8‐trimethyl‐deca‐4(E),6(E)‐dienoic acid (Adda), which is thought to be significant for the activity. Geometrical isomers at C‐7 in the Adda portion of microcystins, 6(Z)‐Adda microcystins LR and RR, have been isolated from cyanohacteria. To estimate their tumor‐promoting activities and to understand the importance of the Adda portion for activity, the maternal microcystins LR and RR and their isomers were subjected to examination of their interaction with protein phosphatases 1 and 2A and the release of glutamic pyruvic transaminase from rat liver. 6(Z)‐Adda microcystins LR and RR bound to protein phosphatases 1 and 2A, inhibited their activities and released glutamic pyruvic transaminase from rat liver into serum, ten to one hundred times more weakly than the maternal microcystins LR and RR. These results indicated that the conjugated diene with 4(E),6(E) geometry in the Adda portion is important in the interaction with protein phosphatases.
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spelling pubmed-59185972018-05-11 Structure‐Function Relationships of Microcystins, Liver Tumor Promoters, in Interaction with Protein Phosphatase Nishiwaki‐Matsushima, Rie Nishiwaki, Shinji Ohta, Tetsuya Yoshizawa, Seiji Suganuma, Masami Harada, Ken‐ichi Watanabe, Mariyo F. Fujiki, Hirota Jpn J Cancer Res Article Microcystins, isolated from toxic blue‐green algae, are potent inhibitors of protein phosphatases 1 and 2A. Recently, we have reported that mierocystin LR has a potent tumor‐promoting activity on rat liver initiated with diethylnitrosamine. The structure of microcystins is unique in having an unusual ammo acid, 3‐amino‐9‐methoxy‐10‐phenyl‐2,6,8‐trimethyl‐deca‐4(E),6(E)‐dienoic acid (Adda), which is thought to be significant for the activity. Geometrical isomers at C‐7 in the Adda portion of microcystins, 6(Z)‐Adda microcystins LR and RR, have been isolated from cyanohacteria. To estimate their tumor‐promoting activities and to understand the importance of the Adda portion for activity, the maternal microcystins LR and RR and their isomers were subjected to examination of their interaction with protein phosphatases 1 and 2A and the release of glutamic pyruvic transaminase from rat liver. 6(Z)‐Adda microcystins LR and RR bound to protein phosphatases 1 and 2A, inhibited their activities and released glutamic pyruvic transaminase from rat liver into serum, ten to one hundred times more weakly than the maternal microcystins LR and RR. These results indicated that the conjugated diene with 4(E),6(E) geometry in the Adda portion is important in the interaction with protein phosphatases. Blackwell Publishing Ltd 1991-09 /pmc/articles/PMC5918597/ /pubmed/1657848 http://dx.doi.org/10.1111/j.1349-7006.1991.tb01933.x Text en
spellingShingle Article
Nishiwaki‐Matsushima, Rie
Nishiwaki, Shinji
Ohta, Tetsuya
Yoshizawa, Seiji
Suganuma, Masami
Harada, Ken‐ichi
Watanabe, Mariyo F.
Fujiki, Hirota
Structure‐Function Relationships of Microcystins, Liver Tumor Promoters, in Interaction with Protein Phosphatase
title Structure‐Function Relationships of Microcystins, Liver Tumor Promoters, in Interaction with Protein Phosphatase
title_full Structure‐Function Relationships of Microcystins, Liver Tumor Promoters, in Interaction with Protein Phosphatase
title_fullStr Structure‐Function Relationships of Microcystins, Liver Tumor Promoters, in Interaction with Protein Phosphatase
title_full_unstemmed Structure‐Function Relationships of Microcystins, Liver Tumor Promoters, in Interaction with Protein Phosphatase
title_short Structure‐Function Relationships of Microcystins, Liver Tumor Promoters, in Interaction with Protein Phosphatase
title_sort structure‐function relationships of microcystins, liver tumor promoters, in interaction with protein phosphatase
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5918597/
https://www.ncbi.nlm.nih.gov/pubmed/1657848
http://dx.doi.org/10.1111/j.1349-7006.1991.tb01933.x
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