Characterization of htAKR, a novel gene product in the aldo-keto reductase family specifically expressed in human testis.
In human testis, expression of a novel member of the aldo-keto reductase family was identified. Based on its testis-specific expression, we termed this protein human testis aldo-keto reductase (htAKR). In addition to four major isoforms, the existence of multiple alternatively spliced products of htAKR was detected using RT-PCR followed by nested PCR. htAKR was a homologue of mouse liver keto-reductase, AKR1E1, with close similarity in their genomic organizations. htAKR4, the longest isoform, was expressed as a non-fused native form. It exhibited a limited activity toward 9,10-phenanthrenequinone, while no activity toward the steroids or prostaglandins was demonstrated. Using the laser capture microdissection technique and RT-PCR, expression of htAKR was detected in testicular germ cells as well as in interstitial cells. The levels of htAKR mRNA in the tissues obtained from seminoma were much lower than those in normal testes. A significant decline in the htAKR expression was observed when NEC8, a cell line originated from a human testicular germ cell tumour, was exposed to phorbol 12-myristate 13-acetate or 5alpha-dihydrotestosterone. These results indicate that the expression of htAKR, down-regulated in the testicular tumour, is possibly controlled by mitogenic and hormonal signals.
Azuma
Yutaro
Y
Department of Pharmacology, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602-8566, Japan.
Nishinaka
Toru
T
Ushijima
So
S
Soh
Jintetsu
J
Katsuyama
Masato
M
Lu
Hai-Ping
HP
Kawata
Mitsuhiro
M
Yabe-Nishimura
Chihiro
C
Miki
Tsuneharu
T
D000429:Alcohol Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000449:Aldehyde Reductase / Q000235:genetics; D000074408:Aldo-Keto Reductases; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D005854:Germ Cells / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D018239:Seminoma / Q000378:metabolism; D016415:Sequence Alignment; D013736:Testicular Neoplasms / Q000378:metabolism; D013737:Testis / Q000166:cytology / Q000502:physiology*
D007527:Isoenzymes; D011994:Recombinant Proteins; D000429:Alcohol Oxidoreductases; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; C000614209:AKR7A5 protein, mouse