Injury-induced "switch" from GTP-regulated to novel GTP-independent isoform of tissue transglutaminase in the rat spinal cord.

Abstract:

: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.

journal_name

J Neurochem

authors

Festoff BW,SantaCruz K,Arnold PM,Sebastian CT,Davies PJ,Citron BA

doi

10.1046/j.1471-4159.2002.00850.x

keywords:

subject

Has Abstract

pub_date

2002-05-01 00:00:00

pages

708-18

issue

4

eissn

0022-3042

issn

1471-4159

journal_volume

81

pub_type

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