Superactivation of transglutaminase type 2 without change in enzyme level occurs during progressive neurodegeneration in the mnd mouse mutant

• Published in: Neuroscience letters 1996-08, Vol.213 (3), p.185-188
• Main Authors: Holmes, Fiona E., Haynes, Laurence W.
• Format: Article
• Language: English
• Subjects: Age Factors; Animals; Apoptosis; Apoptosis - physiology; Biochemistry and metabolism; Biological and medical sciences; Blotting, Western; Central nervous system; Central Nervous System - cytology; Central Nervous System - enzymology; Cross-Linking Reagents - metabolism; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Immunohistochemistry; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; mnd mouse mutant; Motor neuron; Motor Neurons - cytology; Motor Neurons - enzymology; Mutation - physiology; Nerve Degeneration - physiology; Neurodegeneration; Neuropeptides - analysis; Protein cross-linking; Transglutaminase; Transglutaminases - analysis; Transglutaminases - immunology; Transglutaminases - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/0304-3940(96)12855-X

We have investigated the activity of the Ca 2+-dependent apoptosis-related enzyme 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 ϵ ( γ-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.