The mutation Ser511Asn leads to N-glycosylation and increases the cleavage of high molecular weight kininogen in rats genetically susceptible to inflammation

摘要: Crohn disease is immunologically mediated and characterized by intestinal systemic chronic inflammation. In a rat model, injection of peptidoglycan-polysaccharide complexes into the wall induced inflammation in Lewis but neither Fischer nor Buffalo rats, indicating differential genetic susceptibility. Proteolysis plasma high molecular weight kininogen (HK) yielding bradykinin cleaved HK (HKa) was faster than or plasma. A single point mutation at nucleotide 1586 found translating from Ser511 (Buffalo Fisher) to Asn511 (Lewis). The latter defines an Asn-Xaa-Thr consensus sequence for N-glycosylation. We expressed these domains Escherichia coli no differences rate cleavage purified kallikrein 3 strains absence then Chinese hamster ovary (CHO) cells, which are capable glycosylation, increased HK. associated with N-glycosylation as evidenced more rapid migration after treatment N-glycosidase F. When CHO cells were cultured presence tunicamycin, kallikrein-induced not increased. This alteration might be one contributing factor resulting rats.