Increased production of tumor necrosis factor-alpha induces apoptosis after traumatic spinal cord injury in rats
| Autor: | Tae Y. Yune, Tae H. Oh, Song W. Shin, Mi J. Chang, Young Choong Kim, Young J. Oh, Sun J Kim, Ching T. Han, Young Bok Lee, Hyewhon Rhim, George J. Markelonis, Moon L. Shin |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Pathology medicine.medical_specialty Time Factors Nerve Crush Nitric Oxide Synthase Type II Apoptosis DNA laddering Nitric Oxide Antibodies Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Downregulation and upregulation medicine Animals Spinal cord injury Spinal Cord Injuries TUNEL assay business.industry Tumor Necrosis Factor-alpha Spinal cord medicine.disease Molecular biology Rats medicine.anatomical_structure chemistry Enzyme Induction Tumor necrosis factor alpha Neurology (clinical) Nitric Oxide Synthase business |
| Zdroj: | Journal of neurotrauma. 20(2) |
| ISSN: | 0897-7151 |
| Popis: | We showed previously that, after spinal cord injury (SCI), tumor necrosis factor-alpha (TNF-alpha) may serve as an external signal, initiating apoptosis in neurons and oligodendrocytes. To further characterize the apoptotic cascade initiated by TNF-alpha after SCI, we examined the expression of TNF-alpha, inducible nitric oxide (NO) synthase (iNOS), and the level of NO after SCI. Western blots and reverse transcription polymerase chain reactions showed an early upregulation of TNF-alpha after injury. A peak TNF-alpha expression was observed within 1 h of injury. By 4 h after injury, the expression of iNOS and the level of NO were markedly increased in the injured spinal cord. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL)-positive cells were also first observed in the lesioned area 4 h after SCI. The largest number of TUNEL-positive cells was observed between 24-48 h after SCI. Injecting a neutralizing antibody against TNF-alpha into the lesion site after injury significantly reduced the expression of iNOS, the level of NO and the number of TUNEL-positive cells in the injured spinal cord. Injecting the NOS inhibitors, N(G)-monomethyl-L-arginine monoacetate and S-methylisothiourea sulfate, or an NO scavenger, carboxy-PTIO, into the lesion site also significantly reduced the level of NO and the degree of DNA laddering in the injured spinal cord. These data suggest that after SCI, apoptosis induced by TNF-alpha may be mediated in part by NO via upregulation of iNOS, induced in response to TNF-alpha. |
| Databáze: | OpenAIRE |
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