Injury-induced "switch" from GTP-regulated to novel GTP-independent isoform of tissue transglutaminase in the rat spinal cord.
We recently found that alternative transcripts of tissue transglutaminase (tTG or TG2) were present in hippocampal brain regions of Alzheimer's disease (AD), but not in control, non-demented, age-matched brains. Since antecedent non-severe trauma has been implicated in AD and other neurodegenerative diseases, such as Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS), we were interested in whether alternative transcripts might be detected in a model of neurotrauma, controlled-contusion spinal cord injury (SCI) in the rat. Implicated in diverse roles from growth and differentiation to apoptotic cell death, only bifunctional tTG, of the nine member TG family, has dual catalytic activities: guanine trinucleotide (GTP) hydrolyzing activity (GTPase), as well as protein cross-linking. These functions imply two physiological functions: programmed cell life and death. These may have profound roles in the nervous system since studies in cultured astrocytes found tTG short (S) mRNA transcripts induced by treatment with injury-related cytokines. In the developing rat spinal cord, tTG activity is concentrated in ventral horn alpha motoneurons, but neither studies of spinal cord tTG gene expression, nor evaluation of the GTP-regulated isoforms in tissues, have been reported. We now report increased tTG protein and gene expression occurring rapidly after SCI. In parallel, novel appearance of a second, short form transcript, in addition to the normal long (L) isoform, occurs by 8 h of injury. Up-regulation of tTG message and activity following neural injury. with appearance of a truncated GTP-unregulated S form, may represent new approaches to drug targets in neurotrauma.
Festoff
Barry W
BW
Neurobiology Research Laboratory, Department of Veterans Affairs Medical Center, University of Kansas, 4801 Linwood Blvd., Kansas City, MO 64128, USA. bfestoff@kumc.edu
SantaCruz
Karen
K
Arnold
Paul M
PM
Sebastian
Cyril T
CT
Davies
Peter J A
PJ
Citron
Bruce A
BA
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D004195:Disease Models, Animal; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D013119:Spinal Cord Injuries / Q000378:metabolism*; D011503:Transglutaminases / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014949:Wounds, Nonpenetrating
D020033:Protein Isoforms; D012333:RNA, Messenger; C000717609:Tgm2 protein, rat; D006160:Guanosine Triphosphate; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins