Abstract
We have developed a simple system for the sensitive detection and measurement of glutathione S-transferase (GST) activity that detoxifies polycyclic aromatic hydrocarbons using the cultured rat normal liver epithelial cell line, RL34 cells. Citral (3,7-dimethyl-2,6-octadienal) was isolated from the methanol extract of lemongrass (Cymbopogon citratus) and identified as a novel inducer of GST. Citral, a mixture of the two stereoisomers geranial and neral, dose- and time-dependently induced the total and pi-class-specific activities of GST. The structure-activity relationship study revealed that geranial, an E-isomer, was mainly responsible for the inducing activity of citral mixture and the aldehyde group conjugated with a trans-double bond is an essential structural factor. The data were consistent with the in vitro observation that both glutathione (GSH) and protein thiol quickly and specifically reacted with the active isomer geranial, but not neral. Pretreatment of the cells with diethyl maleate significantly enhanced not only the basal activity but also the citral-stimulated activity of GST, while pretreatment with N-acetyl-cysteine inhibited it. Moreover, the treatment of RL 34 cells with geranial for 30min significantly attenuated the intracellular GSH level, while application for 18h enhanced it. These results strongly suggested that the electrophilic property characterized by the reactivity with intracellular nucleophiles including protein thiol or glutathione (GSH) plays an important role in the induction of GST. The present study also implied the antioxidant role of GST induction by citral in mouse skin, providing a new insight into skin cancer prevention.
| Original language | English |
|---|---|
| Pages (from-to) | 593-600 |
| Number of pages | 8 |
| Journal | Biochemical and Biophysical Research Communications |
| Volume | 302 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 14 2003 |
| Externally published | Yes |
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Keywords
- α,β-Unsaturated carbonyl
- Antioxidant
- Cancer prevention
- Citral
- Detoxification
- Electrophile
- Glutathione
- Glutathione S-transferase
- RL34
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Molecular Biology
Cite this
A phase II detoxification enzyme inducer from lemongrass : Identification of citral and involvement of electrophilic reaction in the enzyme induction. / Nakamura, Yoshimasa; Miyamoto, Masaaki; Murakami, Akira; Ohigashi, Hajime; Osawa, Toshihiko; Uchida, Koji.
In: Biochemical and Biophysical Research Communications, Vol. 302, No. 3, 14.03.2003, p. 593-600.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - A phase II detoxification enzyme inducer from lemongrass
T2 - Identification of citral and involvement of electrophilic reaction in the enzyme induction
AU - Nakamura, Yoshimasa
AU - Miyamoto, Masaaki
AU - Murakami, Akira
AU - Ohigashi, Hajime
AU - Osawa, Toshihiko
AU - Uchida, Koji
PY - 2003/3/14
Y1 - 2003/3/14
N2 - We have developed a simple system for the sensitive detection and measurement of glutathione S-transferase (GST) activity that detoxifies polycyclic aromatic hydrocarbons using the cultured rat normal liver epithelial cell line, RL34 cells. Citral (3,7-dimethyl-2,6-octadienal) was isolated from the methanol extract of lemongrass (Cymbopogon citratus) and identified as a novel inducer of GST. Citral, a mixture of the two stereoisomers geranial and neral, dose- and time-dependently induced the total and pi-class-specific activities of GST. The structure-activity relationship study revealed that geranial, an E-isomer, was mainly responsible for the inducing activity of citral mixture and the aldehyde group conjugated with a trans-double bond is an essential structural factor. The data were consistent with the in vitro observation that both glutathione (GSH) and protein thiol quickly and specifically reacted with the active isomer geranial, but not neral. Pretreatment of the cells with diethyl maleate significantly enhanced not only the basal activity but also the citral-stimulated activity of GST, while pretreatment with N-acetyl-cysteine inhibited it. Moreover, the treatment of RL 34 cells with geranial for 30min significantly attenuated the intracellular GSH level, while application for 18h enhanced it. These results strongly suggested that the electrophilic property characterized by the reactivity with intracellular nucleophiles including protein thiol or glutathione (GSH) plays an important role in the induction of GST. The present study also implied the antioxidant role of GST induction by citral in mouse skin, providing a new insight into skin cancer prevention.
AB - We have developed a simple system for the sensitive detection and measurement of glutathione S-transferase (GST) activity that detoxifies polycyclic aromatic hydrocarbons using the cultured rat normal liver epithelial cell line, RL34 cells. Citral (3,7-dimethyl-2,6-octadienal) was isolated from the methanol extract of lemongrass (Cymbopogon citratus) and identified as a novel inducer of GST. Citral, a mixture of the two stereoisomers geranial and neral, dose- and time-dependently induced the total and pi-class-specific activities of GST. The structure-activity relationship study revealed that geranial, an E-isomer, was mainly responsible for the inducing activity of citral mixture and the aldehyde group conjugated with a trans-double bond is an essential structural factor. The data were consistent with the in vitro observation that both glutathione (GSH) and protein thiol quickly and specifically reacted with the active isomer geranial, but not neral. Pretreatment of the cells with diethyl maleate significantly enhanced not only the basal activity but also the citral-stimulated activity of GST, while pretreatment with N-acetyl-cysteine inhibited it. Moreover, the treatment of RL 34 cells with geranial for 30min significantly attenuated the intracellular GSH level, while application for 18h enhanced it. These results strongly suggested that the electrophilic property characterized by the reactivity with intracellular nucleophiles including protein thiol or glutathione (GSH) plays an important role in the induction of GST. The present study also implied the antioxidant role of GST induction by citral in mouse skin, providing a new insight into skin cancer prevention.
KW - α,β-Unsaturated carbonyl
KW - Antioxidant
KW - Cancer prevention
KW - Citral
KW - Detoxification
KW - Electrophile
KW - Glutathione
KW - Glutathione S-transferase
KW - RL34
UR - http://www.scopus.com/inward/record.url?scp=0344406974&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0344406974&partnerID=8YFLogxK
U2 - 10.1016/S0006-291X(03)00219-5
DO - 10.1016/S0006-291X(03)00219-5
M3 - Article
C2 - 12615076
AN - SCOPUS:0344406974
VL - 302
SP - 593
EP - 600
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 3
ER -