Nomenclature for human glutathione transferases

Mannervik, Bengt; Awasthi, Yogesh C.; Board, Philip G.; Hayes, John D.; Ilio, Carmine Di; Ketterer, Brian; Listowsky, Irving; Morgenstern, Ralf; Muramatsu, Masami; Pearson, William R.; Pickett, C.B.; Sato, Kei; Widersten, Mikael; Wolf, C. Roland

doi:10.1042/bj2820305

Cited by 629 publications

(320 citation statements)

References 16 publications

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“…Glutathione-S-transferases (GST) are known to function in antioxidant pathways and in detoxification, and thus might play an important role in protection of the cochlea. GST consists of several gene classes, including GSTM and GSTT, coding for cytosolic enzymes [54,55]. GSTM1 and GSTT1 genes show genetic variability in humans.…”

Section: Oxidative Stressmentioning

confidence: 99%

Ageing and hearing loss

Yan

2007

The Journal of Pathology

258

175

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Although many adults retain good hearing as they age, hearing loss associated with ageing is common among elderly persons. There are a number of pathophysiolological processes underlying age-related changes to functional components in the inner ear. Genetic factors determine the ageing process but are under the influence of intrinsic and environmental factors. It is difficult to distinguish changes of normal ageing from those of other contributing factors. The effects of age-related deafness can have significant physical, functional and mental health consequences. Although a deficit in hearing can be corrected to some degree by a hearing aid or other appropriate amplification devices, hearing-related rehabilitative needs are much more than simply amplifying external sound. Only by better understanding the process of ageing and its effect on the auditory function can we better accommodate elderly people in our day-to-day interactions. We review here the structure and function of the inner ear, pathophysiology associated with age-related hearing loss (ARHL), heritability, allelism and modifier genes of ARHL, and evaluate the genetic analyses for identification of genetic factors that are involved.

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Section: Oxidative Stressmentioning

confidence: 99%

Ageing and hearing loss

Yan

2007

The Journal of Pathology

258

175

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“…To date, the nucleotide sequences of the complete human GST Pi cDNA and GST Pi gene reported from different laboratories (23)(24)(25)(26) have been identical, leading to the notion that only one human GST Pi gene exists (5). The isolation of two different GST Pi proteins from human placenta (27), however, strongly indicates that genetic polymorphism may exist in the human GST Pi gene locus.…”

mentioning

confidence: 94%

“…Three clones, Pi 3A-7, Pi 3B-2, and Pi 3C-9, corresponding to each of three GST Pi mRNA variants, were obtained containing full-length GST Pi cDNAs and including both 5Ј-and 3Ј-termini. The cDNAs were designated hGSTP1*A, hGSTP1*B, and hGSTP1*C, in accordance with the proposed nomenclature for allelic GST gene variants (5). The nucleotide transitions giving rise to the three cDNA variants are shown in the sequence autoradiographs in Fig.…”

Section: Isolation and Sequencing Of Variant Gst Pi Cdnamentioning

confidence: 99%

Molecular Cloning, Characterization, and Expression in Escherichia coli of Full-length cDNAs of Three Human Glutathione S-Transferase Pi Gene Variants

Ali‐Osman

Akande

Antoun

et al. 1997

Journal of Biological Chemistry

620

449

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We report the isolation of three full-length cDNAs corresponding to the mRNAs of closely related glutathione S-transferase (GST) Pi genes, designated hGSTP1*A, hGSTP1*B, and hGSTP1*C, expressed in normal cells and malignant gliomas. The variant cDNAs result from A 3 G and C 3 T transitions at nucleotides ؉313 and ؉341, respectively. The transitions changed codon 104 from ATC (Ile) in hGSTP1*A to GTC (Val) in hGSTP1*B and hGSTP1*C and changed codon 113 from GCG (Ala) to GTG (Val) in hGSTP1*C. Both amino changes are in the electrophile-binding active site of the GST Pi peptide. Computer modeling of the deduced crystal structures of the encoded peptides showed significant deviations in the interatomic distances of critical electrophile-binding active site amino acids as a consequence of the amino acid changes. The encoded proteins expressed in Escherichia coli and purified by GSH affinity chromatography showed a 3-fold lower K m (CDNB) and a 3-4-fold higher K cat /K m for the hGSTP1*A encoded protein than the proteins encoded by hGSTP1*B and hGSTP1*C. Analysis of 75 cases showed the relative frequency of hGSTP1*C to be 4-fold higher in malignant gliomas than in normal tissues. These data provide conclusive molecular evidence of allelopolymorphism of the human GST Pi gene locus, resulting in active, functionally different GST Pi proteins, and should facilitate studies of the role of this gene in xenobiotic metabolism, cancer, and other human diseases.

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“…GSTs function as dimers by catalyzing the conjugation of mutagenic electrophilic substrates to glutathione. In humans, 4 major subfamilies of GSTs can be distinguished and are designated as GSTa, GSTμ, GSTu, and GSTp (Mannervik et al, 1992). Each of these subfamilies is composed of several members, some of which display genetic polymorphism.…”

Section: Introductionmentioning

confidence: 99%