Mouse glutamate carboxypeptidaseII (GCPII) has a similar enzyme activity and inhibition profile but a different tissue distribution to human GCPII

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F17%3A00479478" target="_blank" >RIV/61388963:_____/17:00479478 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11110/17:10362552 RIV/00216208:11120/17:43915516 RIV/00216208:11310/17:10362552

Result on the web

<a href="http://onlinelibrary.wiley.com/doi/10.1002/2211-5463.12276/full" target="_blank" >http://onlinelibrary.wiley.com/doi/10.1002/2211-5463.12276/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/2211-5463.12276" target="_blank" >10.1002/2211-5463.12276</a>

Result language

angličtina

Original language name

Mouse glutamate carboxypeptidaseII (GCPII) has a similar enzyme activity and inhibition profile but a different tissue distribution to human GCPII

Original language description

Glutamate carboxypeptidaseII (GCPII), also known as prostate-specific membrane antigen (PSMA) or folate hydrolase, is a metallopeptidase expressed predominantly in the human brain and prostate. GCPII expression is considerably increased in prostate carcinoma, and the enzyme also participates in glutamate excitotoxicity in the brain. Therefore, GCPII represents an important diagnostic marker of prostate cancer progression and a putative target for the treatment of both prostate cancer and neuronal disorders associated with glutamate excitotoxicity. For the development of novel therapeutics, mouse models are widely used. However, although mouse GCPII activity has been characterized, a detailed comparison of the enzymatic activity and tissue distribution of the mouse and human GCPII orthologs remains lacking. In this study, we prepared extracellular mouse GCPII and compared it with human GCPII. We found that mouse GCPII possesses lower catalytic efficiency but similar substrate specificity compared with the human protein. Using a panel of GCPII inhibitors, we discovered that inhibition constants are generally similar for mouse and human GCPII. Furthermore, we observed highest expression of GCPII protein in the mouse kidney, brain, and salivary glands. Importantly, we did not detect GCPII in the mouse prostate. Our data suggest that the differences in enzymatic activity and inhibition profile are rather small, therefore, mouse GCPII can approximate human GCPII in drug development and testing. On the other hand, significant differences in GCPII tissue expression must be taken into account when developing novel GCPII-based anticancer and therapeutic methods, including targeted anticancer drug delivery systems, and when using mice as a model organism.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2017

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

FEBS Open Bio

ISSN

2211-5463

e-ISSN

—

Volume of the periodical

7

Issue of the periodical within the volume

9

Country of publishing house

GB - UNITED KINGDOM

Number of pages

17

Pages from-to

1362-1378

UT code for WoS article

000409330100012

EID of the result in the Scopus database

2-s2.0-85030673805