Transglutaminase-catalyzed protein cross-linking in the molecular program of apoptosis and its relationship to neuronal processes.

1. One type of transglutaminase is usually accumulated in various forms of naturally occurring cell death and apoptosis. The accumulated enzyme is activated during the death process, leading to the formation of cross-linked protein structures. Degradation of the cross-linked apoptotic bodies results in the elevation of the epsilon (gamma-glutamyl)lysine isodipeptide concentration in body fluids, which may provide a diagnostic tool to monitor the apoptosis rate in various tissues under normal and pathologic conditions. 2. Extensive protein cross-linking may be directly related to the act of killing in some cells. In others, the effect of protein cross-linking is palliative, preventing leakage of macromolecules and enhancing phagocytosis of the dead cells. 3. Tissue transglutaminase has been implicated in some physiologic functions of the nervous system. 4. The molecular machinery of apoptosis is present and easily evoked in neuronal cells. 5. Effector elements of the apoptosis process have been associated with the pathogenesis of neurologic disorders. Tissue transglutaminase, representing one of the effector elements of apoptosis, may be induced and activated in cells following ischemia. It may also participate in the formation of abnormal cell inclusions and A beta deposits in amyloid plaques.