Theta, a new class of glutathione transferases purified from rat and man

Meyer, David J.; Coles, Brian; Pemble, Sally; Gilmore, K S; Fraser, Gerald; Ketterer, Brian

doi:10.1042/bj2740409

Cited by 733 publications

(448 citation statements)

References 16 publications

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“…The ratio of 1,2-epoxy-3-(p-nitrophenoxy)-propane to dichloromethane dehalogenase activity was 16.8, consistent with that recorded by Meyer et al (1991). DCMD DM4 was purified as specified by Scholtz et al (1988).…”

Section: Protein Purificationsupporting

confidence: 71%

“…Polyclonal rabbit antisera to theta 5 GST were a gift from Meyer et al (1991) and polyclonal goat antisera to human MIF (Weiser et al, 1989) were a gift from Dr. Monica Tsang of R&D Systems (Minneapolis, Minnesota). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis was run with Gradient 8-25'" gels in conjunction with Pharmacia LKB's PhastSystem'".…”

Section: Immunochemistrymentioning

confidence: 99%

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MIF proteins are theta‐class glutathione S‐transferase homologs

1993

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MIF proteins are mammalian polypeptides of approximately 13,000 molecular weight. This class includes human macrophage migration inhibitory factor (MIF), a rat liver protein that has glutathione S-transferase (GST) activity (TRANSMIF), and the mouse delayed early response gene 6 (DER6) protein. MIF proteins were previously linked to GSTs by demonstrating transferase activity and observing N-terminal sequence homology with a mu-class GST (Blocki, EA., Schlievert, P.M., & Wackett, L.P., 1992, Nature360, 269-270). In this study, MIF proteins are shown to be structurally related to the theta class of GSTs. This is established in three ways. First, unique primary sequence patterns are developed for each of the GST gene classes. The patterns identify the three MIF proteins as theta-like transferase homologs. Second, pattern analysis indicates that GST members of the theta class contain a serine residue in place of the N-terminal tyrosine that is implicated in glutathione deprotonation and activation in GSTs of known structure (Liu, S., et al., 1992, J. Biol. Chem. 267, 4296-4299). The MIF proteins contain a threonine at this position. Third, polyclonal antibodies raised against recombinant human MIF crossreact on Western blots with rat theta GST but not with alpha and mu GSTs. That MIF proteins have glutathionebinding ability may provide a common structural key toward understanding the varied functions of this widely distributed emerging gene family. Because theta is thought to be the most ancient evolutionary GST class, MIF proteins may have diverged early in evolution but retained a glutathione-binding domain.

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Section: Protein Purificationsupporting

confidence: 71%

Section: Immunochemistrymentioning

confidence: 99%

MIF proteins are theta‐class glutathione S‐transferase homologs

1993

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“…Based on structural, physicochemical, enzymatic and immunological properties, cytosolic GSTs are divided into three classes: a, jL t and % (8). Recently a fourth class of GST (0) has been described (10). The predominant form present in most investigated human tumours is class % GST and comparison of matched pairs of normal and malignant tissues revealed elevated levels in stomach, colon, bladder, cervix and lung tumours (9,(11)(12)(13).…”

Section: © Oxford University Pressmentioning

confidence: 99%

Glutathione S-transferases and glutathione in human head and neck cancer

Mulder¹,

Manni

Roelofs³

et al. 1995

Carcinogenesis

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Glutathione S-transferase (GST) enzyme activity, GST isoenzyme composition and glutathione (GSH) concentra tion were assessed in normal and squamous cell carcinoma specimens of 14 patients with oral or oropharyngeal cancer and 11 patients with laryngeal cancer. Comparing malig nant with normal oral/oropharyngeal tissues, no significant differences in GSH content, GST enzyme activity or iso enzyme composition were found. However, some tumours had up to 3-fold increased GST enzyme activities and 11 malignant samples over-expressed GST-tc. GST-tc was present in all normal and malignant oral/oropharyngeal specimens investigated, whereas class a and class \i were detected in only a few samples. GST-fj. was present in 28% of the patients with oral/oropharyngeal tumours as compared with -60% in the normal population. GST-a, -|i and -71 were detected in 91, 64 and 100% of the normal laryngeal tissues respectively. In laryngeal tumours signi ficantly higher levels of GST-tc and GSH but signi ficantly lower amounts of GST-a were detected. Levels of class p GST were generally lower in cancerous tissues, but differences were not significant. In comparison with normal oral/oropharyngeal tissues, normal laryngeal tissues con tained almost twice the amount of GST enzyme activity due to higher class a enzyme levels. It is concluded that (ÏST-7C is elevated in 11 out of 14 tumours of the oral cavity and values are significantly increased in tumours of the larynx, which may contribute to the inherent anti-cancer drug resistance of these malignancies. In laryngeal tumours the increased GSH levels may confer additional resistance to radiation therapy.

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“…Important drug metabolizing or detoxi fication enzymes are glutathione S-transferases (GST*; EC 2.5.1.18), a family of isozymes divided into three main classes, a, 7T and ]i (10)(11)(12). Recently a fourth class 0 has been described in human and rat liver (13). GSTs catalyze the reaction of a wide variety of electrophiles with glutathione (GSH).…”

Section: Introductionmentioning

confidence: 99%

Effects of consumption of Brussels sprouts on intestinal and lymphocytic glutathione S-transferases in humans

et al. 1995

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A high intake of glucosinolate-containing cruciferous vege tables, such as Brussels sprouts (Brassica oleraceae), has been linked to a decreased cancer risk, but the underlying mechanism is still unclear. The aim of this study was to reveal possible modulating effects of consumption of Brussels sprouts on duodenal, rectal and lymphocytic (i) glutathione S-transferase (GST) enzyme activity, (ii) GST isozyme levels and (iii) glutathione (GSH) content. Ten healthy non-smoking volunteers were randomly assigned to two groups in a cross-over design. Five persons started on a glucosinolate-free diet (control period), while the other five consumed 300 g/day cooked Brussels sprouts, at the expense of 300 g glucosinolate-free vegetables (sprouts period). After 7 days the regimen was changed for a further week. At the end of both periods blood samples and duodenal and rectal biopsies were taken. Mean GST activity showed marked differences between duodenal, rectal and lymphocytic cytosols (737 ± 54, 321 ± 29 and 154 ± 14 nmol/min/mg protein respectively), but was uninfluenced by the dietary regimen. Isozyme distribution varied greatly between the tissues. In duodenum GST-a, -7C and -[i iso zymes were expressed in considerable amounts (8441 ± 1365,3002 ± 223 and 536 ± 248 ng/mg protein respectively). Rectal biopsies also contained above three GST classes, but here GST-n was the most pronounced expressed isozyme (2849 ± 246) followed by GST-|n (495 ± 242), while GSTa was only present in minor quantities (149 ± 31). In lymphocytes only GST-71; (755 ± 96) and GST-p, (83 ± 54) could be detected. As a result of the dietary regimen rectal GST-a and -71 levels were slightly increased at the end of the sprouts period, by 30 and 15% respectively. GSH contents were uninfluenced by the dietary regimen. In conclusion, consumption of glucosinolate-containing Brussels sprouts for 1 week results in increased rectal GST-a and -tc isozyme levels. We hypothesize that these enhanced detoxification enzyme levels may partly explain the epidemiological association between a high intake of glucosinolates (cruciferous vegetables) and a decreased risk of colorectal cancer.

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Theta, a new class of glutathione transferases purified from rat and man

Cited by 733 publications

References 16 publications

MIF proteins are theta‐class glutathione S‐transferase homologs

MIF proteins are theta‐class glutathione S‐transferase homologs

Glutathione S-transferases and glutathione in human head and neck cancer

Effects of consumption of Brussels sprouts on intestinal and lymphocytic glutathione S-transferases in humans

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