Novel water-soluble derivatives of docosahexaenoic acid increase diacylglycerol production mediated by phosphatidylcholine-specific phospholipase C

K. Nishio, T. Morikage, T. Ohmori, N. Kubota, Y. Takeda, S. Ohta, K. Yazawa, Kazunaga Yazawa

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The effect of ascorbic acid 6-docosahexaenoate (DHA-VC) on the phospholipase-C-mediated hydrolysis of phosphatidylcholine was investigated. In human non-small cell lung cancer cells (PC-14) exposed to DHA-VC for 24 hr, a dose-dependent increase in phosphatidylcholine-specific phospholipase C (PC-PLC) activity was seen. PC-PLC activity in whole-cell homogenate of PC- 14 cells was increased about 2.5-fold by 2 hr of treatment with DHA-VC (20 μg/ml). Treatment with DHA-VC also augmented PC-PLC activity in the crude membrane extract. On the other hand, DHA-VC inhibited the activity of phospholipase A2 (ID50 = 800 μg/ml). Another water-soluble analog, choline docosahexaenoate, also stimulated PC-PLC activity. To explore the effect of DHA-VC on phosphatidylcholine turnover, we analyzed phospholipids labeled with [14C] choline or [3H]myristate by thin-layer chromatography, and found that the amount of [14C]- and [3H]-labeled phosphatidylcholine was constant in the presence of DHA-VC. These results suggest that phosphatidylcholine turnover was not influenced by DHA-VC. DHA-VC treatment increased protein kinase C activity of the cells in the late phase (120 min), suggesting that DHA-VC-induced diacylglycerol production mediated by PC-PLC causes protein kinase C activation. Considering that significant inhibition of DNA synthesis occurred 12 hr after 2 hr of treatment with DHA-VC (20 μg/ml), DHA-VC-induced PC-PLC activation seems to be an early event in DHA- VC-induced cytotoxicity, which suggests that the effects of DHA-VC on signal transduction pathways may play an important role in the cytotoxicity of DHA- VC.

Original languageEnglish
Pages (from-to)200-208
Number of pages9
JournalProceedings of the Society for Experimental Biology and Medicine
Volume203
Issue number2
Publication statusPublished - 1993
Externally publishedYes

Fingerprint

Docosahexaenoic Acids
Diglycerides
Derivatives
Phosphatidylcholines
Water
Cells
Cytotoxicity
Choline
Protein Kinase C
Chemical activation
Thin layer chromatography
Signal transduction
Phospholipases A2
Myristic Acid
Type C Phospholipases
Thin Layer Chromatography
Complex Mixtures
Non-Small Cell Lung Carcinoma
Ascorbic Acid
phosphatidylcholine-specific phospholipase C

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Novel water-soluble derivatives of docosahexaenoic acid increase diacylglycerol production mediated by phosphatidylcholine-specific phospholipase C. / Nishio, K.; Morikage, T.; Ohmori, T.; Kubota, N.; Takeda, Y.; Ohta, S.; Yazawa, K.; Yazawa, Kazunaga.

In: Proceedings of the Society for Experimental Biology and Medicine, Vol. 203, No. 2, 1993, p. 200-208.

Research output: Contribution to journalArticle

Nishio, K. ; Morikage, T. ; Ohmori, T. ; Kubota, N. ; Takeda, Y. ; Ohta, S. ; Yazawa, K. ; Yazawa, Kazunaga. / Novel water-soluble derivatives of docosahexaenoic acid increase diacylglycerol production mediated by phosphatidylcholine-specific phospholipase C. In: Proceedings of the Society for Experimental Biology and Medicine. 1993 ; Vol. 203, No. 2. pp. 200-208.
@article{d266678bdc1648af8bfbc9a113aa2067,
title = "Novel water-soluble derivatives of docosahexaenoic acid increase diacylglycerol production mediated by phosphatidylcholine-specific phospholipase C",
abstract = "The effect of ascorbic acid 6-docosahexaenoate (DHA-VC) on the phospholipase-C-mediated hydrolysis of phosphatidylcholine was investigated. In human non-small cell lung cancer cells (PC-14) exposed to DHA-VC for 24 hr, a dose-dependent increase in phosphatidylcholine-specific phospholipase C (PC-PLC) activity was seen. PC-PLC activity in whole-cell homogenate of PC- 14 cells was increased about 2.5-fold by 2 hr of treatment with DHA-VC (20 μg/ml). Treatment with DHA-VC also augmented PC-PLC activity in the crude membrane extract. On the other hand, DHA-VC inhibited the activity of phospholipase A2 (ID50 = 800 μg/ml). Another water-soluble analog, choline docosahexaenoate, also stimulated PC-PLC activity. To explore the effect of DHA-VC on phosphatidylcholine turnover, we analyzed phospholipids labeled with [14C] choline or [3H]myristate by thin-layer chromatography, and found that the amount of [14C]- and [3H]-labeled phosphatidylcholine was constant in the presence of DHA-VC. These results suggest that phosphatidylcholine turnover was not influenced by DHA-VC. DHA-VC treatment increased protein kinase C activity of the cells in the late phase (120 min), suggesting that DHA-VC-induced diacylglycerol production mediated by PC-PLC causes protein kinase C activation. Considering that significant inhibition of DNA synthesis occurred 12 hr after 2 hr of treatment with DHA-VC (20 μg/ml), DHA-VC-induced PC-PLC activation seems to be an early event in DHA- VC-induced cytotoxicity, which suggests that the effects of DHA-VC on signal transduction pathways may play an important role in the cytotoxicity of DHA- VC.",
author = "K. Nishio and T. Morikage and T. Ohmori and N. Kubota and Y. Takeda and S. Ohta and K. Yazawa and Kazunaga Yazawa",
year = "1993",
language = "English",
volume = "203",
pages = "200--208",
journal = "Experimental Biology and Medicine",
issn = "1535-3702",
publisher = "SAGE Publications Ltd",
number = "2",

}

TY - JOUR

T1 - Novel water-soluble derivatives of docosahexaenoic acid increase diacylglycerol production mediated by phosphatidylcholine-specific phospholipase C

AU - Nishio, K.

AU - Morikage, T.

AU - Ohmori, T.

AU - Kubota, N.

AU - Takeda, Y.

AU - Ohta, S.

AU - Yazawa, K.

AU - Yazawa, Kazunaga

PY - 1993

Y1 - 1993

N2 - The effect of ascorbic acid 6-docosahexaenoate (DHA-VC) on the phospholipase-C-mediated hydrolysis of phosphatidylcholine was investigated. In human non-small cell lung cancer cells (PC-14) exposed to DHA-VC for 24 hr, a dose-dependent increase in phosphatidylcholine-specific phospholipase C (PC-PLC) activity was seen. PC-PLC activity in whole-cell homogenate of PC- 14 cells was increased about 2.5-fold by 2 hr of treatment with DHA-VC (20 μg/ml). Treatment with DHA-VC also augmented PC-PLC activity in the crude membrane extract. On the other hand, DHA-VC inhibited the activity of phospholipase A2 (ID50 = 800 μg/ml). Another water-soluble analog, choline docosahexaenoate, also stimulated PC-PLC activity. To explore the effect of DHA-VC on phosphatidylcholine turnover, we analyzed phospholipids labeled with [14C] choline or [3H]myristate by thin-layer chromatography, and found that the amount of [14C]- and [3H]-labeled phosphatidylcholine was constant in the presence of DHA-VC. These results suggest that phosphatidylcholine turnover was not influenced by DHA-VC. DHA-VC treatment increased protein kinase C activity of the cells in the late phase (120 min), suggesting that DHA-VC-induced diacylglycerol production mediated by PC-PLC causes protein kinase C activation. Considering that significant inhibition of DNA synthesis occurred 12 hr after 2 hr of treatment with DHA-VC (20 μg/ml), DHA-VC-induced PC-PLC activation seems to be an early event in DHA- VC-induced cytotoxicity, which suggests that the effects of DHA-VC on signal transduction pathways may play an important role in the cytotoxicity of DHA- VC.

AB - The effect of ascorbic acid 6-docosahexaenoate (DHA-VC) on the phospholipase-C-mediated hydrolysis of phosphatidylcholine was investigated. In human non-small cell lung cancer cells (PC-14) exposed to DHA-VC for 24 hr, a dose-dependent increase in phosphatidylcholine-specific phospholipase C (PC-PLC) activity was seen. PC-PLC activity in whole-cell homogenate of PC- 14 cells was increased about 2.5-fold by 2 hr of treatment with DHA-VC (20 μg/ml). Treatment with DHA-VC also augmented PC-PLC activity in the crude membrane extract. On the other hand, DHA-VC inhibited the activity of phospholipase A2 (ID50 = 800 μg/ml). Another water-soluble analog, choline docosahexaenoate, also stimulated PC-PLC activity. To explore the effect of DHA-VC on phosphatidylcholine turnover, we analyzed phospholipids labeled with [14C] choline or [3H]myristate by thin-layer chromatography, and found that the amount of [14C]- and [3H]-labeled phosphatidylcholine was constant in the presence of DHA-VC. These results suggest that phosphatidylcholine turnover was not influenced by DHA-VC. DHA-VC treatment increased protein kinase C activity of the cells in the late phase (120 min), suggesting that DHA-VC-induced diacylglycerol production mediated by PC-PLC causes protein kinase C activation. Considering that significant inhibition of DNA synthesis occurred 12 hr after 2 hr of treatment with DHA-VC (20 μg/ml), DHA-VC-induced PC-PLC activation seems to be an early event in DHA- VC-induced cytotoxicity, which suggests that the effects of DHA-VC on signal transduction pathways may play an important role in the cytotoxicity of DHA- VC.

UR - http://www.scopus.com/inward/record.url?scp=0027189791&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027189791&partnerID=8YFLogxK

M3 - Article

C2 - 8389049

AN - SCOPUS:0027189791

VL - 203

SP - 200

EP - 208

JO - Experimental Biology and Medicine

JF - Experimental Biology and Medicine

SN - 1535-3702

IS - 2

ER -