Transglutaminase in the life and death of the pancreatic β-cell

Tissue transglutaminase (TG2) is a ubiquitous enzyme that catalyses both the Ca2+-dependent formation of protein cross-links via intermolecular isopeptide bonds, and the Ca2+-independent hydrolysis of GTP. The multifunctional nature of the TG2 protein has been reported in numerous intracellular mechanisms, cell-surface associations, and extracellular matrix (ECM) interactions. In the pancreas, the expression of TG may be fundamental to the insulin-secretion function of β-cells, and associated diabetic disorders. The functional roles of TG2 in the pancreas were investigated in the present study using in vitro models of rat pancreatic insulinoma β-cells (BRIN-BD11), and ex vivo islet of Langerhans models from human, rat, TG2(-/-) knockout mice and their wild-type counterparts. The importance of ECM-associated TG2 in the maintenance of β-cell survival and function was also investigated using an in vitro human urinary bladder carcinoma support matrix (5637 cells). Biochemical analysis of both clonal BRIN-BD11 and islet β-cells showed a thiol-dependent TG2 activity mechanism that was reciprocally regulated by Ca2+ and GTP.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

Nottingham Trent University

Year dc:date.issued

2010

Author dc:creator

• Dookie, S

Language dc:language

en