+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

A novel mechanism of glutathione conjugate formation by lipoxygenase: a study with ethacrynic acid

, : A novel mechanism of glutathione conjugate formation by lipoxygenase: a study with ethacrynic acid. Toxicology and Applied Pharmacology 143(1): 179-188

Ethacrynic acid (EA), a diuretic drug, is known to interact with glutathione transferases in the presence of reduced glutathione (GSH) to yield an EA-SG conjugate. Here we present evidence for a new mechanism for the formation of EA-SG conjugate by a soybean lipoxygenase (SLO)-mediated reaction involving oxidation of GSH to a GS. Similar to the glutathione transferase-mediated reaction, EA-SG conjugate generated by SLO exhibited an absorbance maximum at 270 nm. The conjugate formation was dependent on the concentration of linoleic acid, EA, GSH, and SLO. The optimal assay conditions to observe a maximal rate of EA-SG formation required the presence of 0.4 mm linoleic acid, 1 mm GSH, 50 nm SLO, and 0.2 mm EA at pH 9.0. Classical inhibitors of lipoxygenase, e.g., nordihydroguaiaretic acid, gossypol, and 5,8,11-eicosatriynoic acid, significantly inhibited EA-SG conjugation. The SLO-generated EA-SG was isolated as a single peak by HPLC. Quantitation of EA-SG by HPLC-coupled radiometry using (3H)GSH yielded a rate of 16.5 mu-mol/min/mg SLO protein. This rate is up to 1650-fold greater than that reported for different purified isozymes of mammalian glutathione transferase. The structure of EA-SG isolated from HPLC column was confirmed by matrix-assisted laser desorption mass spectroscopy. These results suggest that lipoxygenase, which is primarily known for xenobiotic oxidation, may represent yet another important pathway for GSH conjugate formation that could lead to detoxification of certain chemicals.


PMID: 9073606

DOI: 10.1006/taap.1996.8062

Other references

Moser, S.A.; Elkins, C.A.; Savage, D.C., 2000: Relationship of genes encoding conjugated bile salt hydrolases in lactobacilli and certain other gram-positive intestinal bacteria. Abstracts of the General Meeting of the American Society for Microbiology 100: 377

Segal K.R.; Van Loan M.; Fitzgerald P.I.; Hodgdon J.A.; Van Itallie T.B., 1987: Estimation of lean body mass by bioelectrical impedance a multicenter validation study. Medicine & Science in Sports & Exercise 19(2 SUPPL): S39

Mitra, A.Kumar.; Bandyopadhyay, P.K.; Gong, Y., 2013: Studies on Trichodinid and Chilodonellid Ciliophorans (Protozoa: Ciliophora) in the Indian freshwater and estuarine fishes with description of Trichodinella sunderbanensis sp. nov. and Trichodina nandusi sp. nov. A comprehensive icthyoparasotological survey among estuarine and freshwater fishes of West Bengal, India revealed Trichodinella sunderbanensis sp. nov. and Trichodina acuta Lom, 1961 from an estuarine fish Mystus gulio (Hamilton, 1822) from the Vi...

Pinel Virginie; Jaupart Claude, 2003: Magma chamber behavior beneath a volcanic edifice. Journal of Geophysical Research, B, Solid Earth and Planets 108(2, 2003

Lu, Z.; Kasaragod, D.K.; Matcher, S.J., 2012: Polarization-sensitive optical coherence tomography using continuous polarization modulation with arbitrary phase modulation amplitude. We demonstrate theoretically and experimentally that the phase retardance and relative optic-axis orientation of a sample can be calculated without prior knowledge of the actual value of the phase modulation amplitude when using a polarization-sen...

Armstrong, M.A.; Fraser, K.B.; Dermott, E.; Shirodaria, P.V., 1982: Immunoelectron microscopic studies on haemagglutinin and haemolysin of measles virus in infected HEp2 cells. The antigenic determinants of the hemagglutinin and hemolysin antigens of measles virus were located at the surface of human laryngeal carcinoma of HEp2 cells infected with measles virus and on measles virions released from these celle, using immu...

Scheen, A.J., 2001: Hepatotoxicity with thiazolidinediones: is it a class effect?. Decreased insulin sensitivity plays a major role in various human diseases. particularly type 2 diabetes mellitus, and is associated with a higher risk of atherosclerosis and cardiovascular complications. Thiazolidinediones, more commonly termed g...

Wilson, C.M.; Miller, W.C.; Goh, E.H., 1995: Crocetin increases exercise endurance in rats. FASEB Journal 9(4): A997

Rocha, H.M.; Mariano, A.H., 1969: But J. Selection of cacao cultivars resistant to Phytophthora palmivora. The cvs SCA-6, UF-613, EEG-8, CAS-1 and several SICs of the Catongo series showed considerable resistance to a local P. palmivora strain.

Borrego, F.; Kabat, J.; Kim, D.K.; Lieto, L.; Maasho, K.; Pena, J.; Solana, R.; Coligan, J.E., 2002: Structure and function of major histocompatibility complex class I specific receptors expressed on human natural killer cells. Natural killer (NK) cells express receptors that are specific for MHC class I molecules. These receptors play a crucial role in regulating the lytic and cytokine expression capabilities of NK cells. In humans, three distinct families of genes have...