Superactivation of transglutaminase type 2 without change in enzyme level occurs during progressive neurodegeneration in the mnd mouse mutant.
We have investigated the activity of the Ca(2+)-dependent apoptosis-related transglutaminase type 2 in the mnd/mnd mouse mutant. Transglutaminase activity in mnd/mnd central nervous system (CNS) tissue homogenates was identical to that of healthy animals at 3 months of age, but at 8 months it was greater in the mnd/mnd CNS by up to four times, depending on the region. Western blot analysis showed no difference in the level of immunoreactive transglutaminase type 2 in spinal cord homogenates between mnd/mnd and healthy mice. However, a greater number of acyl donor protein substrates of transglutaminase were identified in mnd/mnd tissue. N epsilon (gamma-Glutamyl)lysine cross-linked product of transglutaminase activity was localized to the soma of degenerating motor neurons in the mnd/mnd mouse spinal cord. We conclude that neurodegeneration in the mnd/mnd mouse is accompanied by activation of transglutaminase at substrate level. Possible mechanisms of activation and its implications for cellular pathology are discussed.
Holmes
F E
FE
School of Biological Sciences, University of Bristol, UK.
Haynes
L W
LW
D000367:Age Factors; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002490:Central Nervous System / Q000166:cytology / Q000201:enzymology; D003432:Cross-Linking Reagents / Q000378:metabolism; D004789:Enzyme Activation; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009046:Motor Neurons / Q000166:cytology / Q000201:enzymology; D009154:Mutation / Q000502:physiology; D009410:Nerve Degeneration / Q000502:physiology*; D009479:Neuropeptides / Q000032:analysis; D011503:Transglutaminases / Q000032:analysis / Q000276:immunology / Q000378:metabolism*
D003432:Cross-Linking Reagents; D009479:Neuropeptides; D011503:Transglutaminases