Sequential expression of c-fos protooncogene, TNF-alpha, and dynorphin genes in spinal cord following experimental traumatic injury.
Reverse transcription-polymerase chain reaction (RT-PCR) was used to estimate dynamic changes in levels of c-fos protooncogene, tumor necrosis factor alpha (TNF-alpha), and preprodynorphin messenger ribonucleic acid (mRNA) isolated from individual segments (T1 to T12) of rat spinal cord following graded impact trauma (50 or 100 g/cm) to the T9 segment of pentobarbital-anesthetized rats. Trauma caused elevation of c-fos mRNA at the trauma site by 30 min after injury that was related to injury severity. At this time, increased levels of TNF-alpha (but not of preprodynorphin) mRNA were also found. By 24 h, c-fos and TNF-alpha mRNA had returned to normal levels at trauma site, but were now increased at more distal segments (T5 and T12). At 4 h after trauma, induction of preprodynorphin mRNA was detected at the trauma site; levels continued to be elevated at 24 h when they were also detected at T5 and T12. Increases for each mRNA were greater for severe as compared to moderate trauma. The injury dose- and time-dependent changes in c-fos, TNF-alpha, and preprodynorphin gene expression suggest that their respective proteins are synthesized in response to trauma, and may play a part in the secondary injury response. Later accumulation of message distant from the trauma site may reflect a progression of delayed damage along the spinal cord.
Yakovlev
A G
AG
Department of Neurology, Georgetown University Medical Center, Washington, DC 20007.
Faden
A I
AI
D000818:Animals; D001483:Base Sequence; D004399:Dynorphins / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression / Q000502:physiology*; D016762:Genes, fos / Q000187:drug effects*; D006657:Histones / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013119:Spinal Cord Injuries / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D006657:Histones; D011498:Protein Precursors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C036448:pre-prodynorphin; D004399:Dynorphins