Neurolysin Knockout Mice Generation and Initial Phenotype Characterization

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Cavalcanti, Diogo M. L. P. ^[1] ; Castro, Leandro M. ^{[2, 3]} ; Rosa Neto, Jose C. ^[1] ; Seelaender, Marilia ^[1] ; Neves, Rodrigo X. ^[1] ; Oliveira, Vitor ^[3] ; Forti, Fabio L. ^[4] ; Iwai, Leo K. ^[5] ; Gozzo, Fabio C. ^[6] ; Todiras, Mihail ^[7] ; Schadock, Ines ^[7] ; Barros, Carlos C. ^{[7, 8]} ; Bader, Michael ^[7] ; Ferro, Emer S. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Cell Biol & Dev, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Support Ctr Res Proteolysis & Cell Signaling, BR-05508900 Sao Paulo - Brazil

^[3] Univ Fed Sao Paulo, Dept Biophys, BR-04039032 Sao Paulo - Brazil

^[4] Univ Sao Paulo, Inst Chem, Dept Biochem, Support Ctr Res Proteolysis & Cell Signaling, BR-05508000 Sao Paulo - Brazil

^[5] Butantan Inst, Special Lab Appl Toxinol, Ctr Toxins Immune Response & Cell Signaling, BR-05503000 Sao Paulo - Brazil

^[6] Univ Estadual Campinas, Inst Chem, BR-13083862 Campinas, SP - Brazil

^[7] Max Delbruck Ctr Mol Med, D-13125 Berlin - Germany

^[8] Univ Fed Pelotas, Dept Nutr, BR-96010610 Pelotas, RS - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Journal of Biological Chemistry; v. 289, n. 22, p. 15426-15440, MAY 30 2014.
• Citações Web of Science: 14

Resumo

The oligopeptidase neurolysin (EC 3.4.24.16; Nln) was first identified in rat brain synaptic membranes and shown to ubiquitously participate in the catabolism of bioactive peptides such as neurotensin and bradykinin. Recently, it was suggested that Nln reduction could improve insulin sensitivity. Here, we have shown that Nln KO mice have increased glucose tolerance, insulin sensitivity, and gluconeogenesis. KO mice have increased liver mRNA for several genes related to gluconeogenesis. Isotopic label semiquantitative peptidomic analysis suggests an increase in specific intracellular peptides in gastrocnemius and epididymal adipose tissue, which likely is involved with the increased glucose tolerance and insulin sensitivity in the KO mice. These results suggest the exciting new possibility that Nln is a key enzyme for energy metabolism and could be a novel therapeutic target to improve glucose uptake and insulin sensitivity. (AU)

• Processo FAPESP: 04/04933-2 - Biologia celular molecular de oligopeptidases
• Beneficiário: Emer Suavinho Ferro
• Modalidade de apoio: Auxílio à Pesquisa - Temático