Disease relevance of SPAG8

• Escherichia coli transfected with the construct containing the alternative 5'-end failed to produce the recombinant product, whereas those transfected with the vector lacking the 5'-end produced hSMP-1 [1].
• Although initial studies in transgenic mice and humans are encouraging, more data are required to conclusively prove the hypothesis that the adipose-tissue-specific overexpression of HSD1 and the resultant increase in tissue-specific cortisol concentrations result in human obesity, insulin resistance, high blood pressure, and metabolic syndrome [2].
• At the cellular level, the enzyme hydroxysteroid dehydrogenase type 1 (HSD1) locally regenerates active cortisol from inactive cortisone, amplifying glucocorticoid receptor activation and promoting preadipocyte differentiation and adipocyte hypertrophy [2].
• RESULTS: In cases of chorioamnionitis where mothers had not been treated with betamethasone, placental 32-kd 11beta HSD-1 protein expression was increased [3].

High impact information on SPAG8

• One of the components, RanBPM, was found to be associated with hSMP-1 under both in vitro and in vivo conditions [4].
• This interaction between hSMP-1 and RanBPM may be involved in the process of male germ cell differentiation [4].
• These findings suggest that hSMP-1 interacts with tubulins and thereby may modulate microtubule assembly and/or activity [4].
• MATERIALS AND METHODS: Sperm membrane proteins were prepared from donor spermatozoa, separated by 1-dimensional polyacrylamide gel electrophoresis and exposed to seminal plasma samples of 36 infertile men and 34 after vasectomy containing antisperm antibodies [5].
• By rescreening human testis cDNA libraries with the HSD-1 insert and using rapid amplification of cDNA ends, the complete cDNA of 2482 bp was identified and sequenced [6].

Biological context of SPAG8

• The availability of large amounts of recombinant hSMP-1 and its antiserum will facilitate studies on the function and expression of the protein during spermatogenesis and the assessment of its potential value as a contraceptive immunogen [6].
• HSD-1 was localized to a single locus on chromosome 9 and assigned to band 9p12-p13 by fluorescent in situ hybridization (FISH) mapping and DAPI (4,6-diamidino-2-phenylindole) banding, using rat/human somatic cell hybrids and metaphase chromosomes of human lymphocytes [1].
• CONCLUSIONS: Our study shows that cortisone reduces glucose uptake in diabetic myotubes and that this effect seems mediated by an increased mRNA HSD1 expression emphasizing that the local conversion of inactive to active glucocorticoids may be important in the pathogenesis of insulin resistance [7].
• Sperm membrane incorporation into oolemma contributes to the oolemma block to sperm penetration: evidence based on intracytoplasmic sperm injection experiments in the mouse [8].
• Measurements (i) 11beta HSD-1 and H6PDH mRNA expression by quantitative reverse transcription polymerase chain reaction (RT-PCR); (ii) protein localization and fibre type specificity by immunohistochemistry; and (iii) enzyme oxoreductase activity by percentage conversion of (3)H cortisone to cortisol [9].

Anatomical context of SPAG8

• The hSMP-1 component was localized on the surface of the head of mature rat spermatozoa by an immunofluorescence technique using polyclonal anti-hSMP-1 antibodies [10].
• H6PDH mRNA was also detected with a mean DeltaC(T) of 14.46 (range 13.13-16.60), approximately 35-fold more abundant than 11beta HSD-1 in skeletal muscle [9].
• Sperm membrane destabilization is believed to occur during chilling of semen, although its effect on the post-thaw (PT) fertility of the spermatozoa has not yet been fully assessed [11].
• HSD activity was examined in human liver (HSD1) and kidney microsomes (HSD2) and in CHO cells stably transfected with both enzymes [12].
• Inhibition of mouse acrosome reaction and sperm-zona pellucida binding by anti-human sperm membrane protein 1 antibody [13].

Associations of SPAG8 with chemical compounds

• 11beta HSD-1 oxoreductase activity was demonstrated, with mean conversion of cortisone to cortisol of 17.7% per 200 mg of muscle per 24 h (range 7.1-29.5%) [9].
• Objective No data exist regarding the distribution and oxoreductase enzyme activity of 11beta hydroxysteroid dehydrogenase type 1 (11beta HSD-1) in fresh human skeletal muscle [9].
• In vivo, hepatic 11beta-hydroxysteroid dehydrogenase 1 (HSD1) stimulates the shift of 11-dehydrocorticosterone to corticosterone, enhancing active glucocorticoids at tissue level [14].
• Sperm membrane features examined included progesterone-induced changes in intracellular levels of calcium ([Ca2+]i), as measured by the fluorescent fura-2 indicator, and the tight binding of spermatozoa to homologous zonae pellucidae as assessed by the hemizona assay (HZA) [15].
• (3) Sperm membrane isolation from the sucrose interface between 0.75 and 1.05 M sucrose was found to be most effective [16].

Other interactions of SPAG8

• Western blotting was used to determine 11beta HSD-1, 11beta HSD-2, GRT, and GRalpha expression, and 11beta HSD-2 activity was determined in each group [3].

Analytical, diagnostic and therapeutic context of SPAG8

• Immunofluorescence data showed that hSMP-1 was localized to the head of human sperm [6].
• However, in cells transfected with pEGFP-Cl-hSMP-1, reassembly of the dispersed tubulins was blocked even upon rewarming of the cells [4].
• Usingan immunocytochemical technique, hSMP-1 protein was immunolocalized in germ cells of human testis at all stages of spermatogenesis. mRNAs were prepared from 16 different human tissues and analyzed by Northern blot using HSD-1 as probe [17].
• Sperm membrane damage during cryopreservation reduces the recovery of motile sperm [18].
• Compared with unstressed controls, all types of stress significantly increased HSD1 activity (146% cannula, 130% NaCl, and 253% HCl), phosphoenolpyruvate carboxykinase activity (51% cannula, 48% NaCl, and 86% HCl), and glycemia (29% cannula, 30% NaCl, and 41% HCl), but decreased hepatic glycogen (68% cannula, 68% NaCl, and 78% HCl) [14].

References