Aim： To investigate the role of a novel dipeptidyl peptidase 8 transcript variant （DPP8-v3） gene in testis development and/or spermatogenesis. Methods： A human testis cDNA microarray was hybridized with mRNA of hu...Aim： To investigate the role of a novel dipeptidyl peptidase 8 transcript variant （DPP8-v3） gene in testis development and/or spermatogenesis. Methods： A human testis cDNA microarray was hybridized with mRNA of human adult and fetal testes. Differentially expressed clones were sequenced and characterized and their expression was analyzed by real-time reverse transcription polymerase chain reaction （RT-PCR） and Southern-blot analysis. Results： A new transcript variant of the human dipeptidyl peptidase （DPP8）, exhibiting a 5-fold higher expression level in human adult than that in fetal testes, was cloned and was named DPP8 variant 3 （DPP8-v3）. The full-length sequence of DPP8-v3 was 3,030 bp, encoding a protein of 898 amino acids. Conclusion： DPPS-v3 is a novel human DPP8 transcript variant highly expressed in the adult testis. Similar to DPPIV, DPP8-v3 may play a key role in the immunoregulation of testes and accordingly may influence spermatogenesis and male fertility. （Asian J Androl 2005 Sep; 7： 245-255）展开更多
Dipeptidyl peptidase 4(DPP4)is recognised as an attractive anti-diabetic drug target,and several DPP4 inhibitors are already on the market.As members of the same gene family,dipeptidyl peptidase 8(DPP8)and dipeptidyl ...Dipeptidyl peptidase 4(DPP4)is recognised as an attractive anti-diabetic drug target,and several DPP4 inhibitors are already on the market.As members of the same gene family,dipeptidyl peptidase 8(DPP8)and dipeptidyl peptidase 9(DPP9)share high sequence and structural homology as well as functional activity with DPP4.However,the inhibition of their activities was reported to cause severe toxicities.Thus,the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic therapy.To achieve this goal,we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta cells.In this method,we used purified recombinant 120 kDa DPP8 or DPP9 protein from the Rosetta expression system.The optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30 ng/mL and 20 ng/mL,respectively,and the corresponding concentrations of their substrates were both 0.2 mmol/L.This method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates,which would provide valuable guidance in the development of safe DPP4 inhibitors.展开更多
文摘Aim： To investigate the role of a novel dipeptidyl peptidase 8 transcript variant （DPP8-v3） gene in testis development and/or spermatogenesis. Methods： A human testis cDNA microarray was hybridized with mRNA of human adult and fetal testes. Differentially expressed clones were sequenced and characterized and their expression was analyzed by real-time reverse transcription polymerase chain reaction （RT-PCR） and Southern-blot analysis. Results： A new transcript variant of the human dipeptidyl peptidase （DPP8）, exhibiting a 5-fold higher expression level in human adult than that in fetal testes, was cloned and was named DPP8 variant 3 （DPP8-v3）. The full-length sequence of DPP8-v3 was 3,030 bp, encoding a protein of 898 amino acids. Conclusion： DPPS-v3 is a novel human DPP8 transcript variant highly expressed in the adult testis. Similar to DPPIV, DPP8-v3 may play a key role in the immunoregulation of testes and accordingly may influence spermatogenesis and male fertility. （Asian J Androl 2005 Sep; 7： 245-255）
基金We greatly appreciate Prof.Haihong Huang and Dr.Bei Han for the chemical synthesis of UAMC00132sitagliptin.This work was supported by a fund from National Mega-project for Innova-tive Drugs(2012ZX09301002-004,China).
文摘Dipeptidyl peptidase 4(DPP4)is recognised as an attractive anti-diabetic drug target,and several DPP4 inhibitors are already on the market.As members of the same gene family,dipeptidyl peptidase 8(DPP8)and dipeptidyl peptidase 9(DPP9)share high sequence and structural homology as well as functional activity with DPP4.However,the inhibition of their activities was reported to cause severe toxicities.Thus,the development of DPP4 inhibitors that do not have DPP8 and DPP9 inhibitory activity is critical for safe anti-diabetic therapy.To achieve this goal,we established a selective evaluation method for DPP4 inhibitors based on recombinant human DPP8 and DPP9 proteins expressed by Rosetta cells.In this method,we used purified recombinant 120 kDa DPP8 or DPP9 protein from the Rosetta expression system.The optimum concentrations of the recombinant DPP8 and DPP9 proteins were 30 ng/mL and 20 ng/mL,respectively,and the corresponding concentrations of their substrates were both 0.2 mmol/L.This method was highly reproducible and reliable for the evaluation of the DPP8 and DPP9 selectivity for DPP4 inhibitor candidates,which would provide valuable guidance in the development of safe DPP4 inhibitors.
