Endotoxin stress-response in cardiomyocytes: NF-κB activation and tumor necrosis factor-α expression
| Autor: | Terry B. Rogers, Allan S. Cross, Gary L. Wright, Jeffery D. Hasday, Gentzon Hall, Ishwar S. Singh, Iain K. Farrance |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Lipopolysaccharides
Cytoplasm Proteasome Endopeptidase Complex medicine.medical_specialty Pyrrolidines Transcription Genetic Lipopolysaccharide Physiology medicine.medical_treatment Blotting Western Cysteine Proteinase Inhibitors Biology Antioxidants Mice chemistry.chemical_compound Multienzyme Complexes Stress Physiological Thiocarbamates Physiology (medical) Internal medicine Gene expression medicine Animals Myocyte Cell Nucleus Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha Myocardium NF-kappa B Heart In vitro Acetylcysteine Endotoxins Cysteine Endopeptidases Endocrinology Cytokine Animals Newborn chemistry Circulatory system Cancer research Tumor necrosis factor alpha Cardiology and Cardiovascular Medicine Intracellular |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 282:H872-H879 |
| ISSN: | 1522-1539 0363-6135 |
| DOI: | 10.1152/ajpheart.00256.2001 |
| Popis: | Although tumor necrosis factor (TNF)-alpha is implicated in numerous cardiac pathologies, the intracellular events leading to its production by heart cells are largely unknown. The goal of the present study was to identify the role of the transcription factor nuclear factor (NF)-kappaB in this process. Among the many inducers of TNF-alpha expression in myeloid cells, only lipopolysaccharide (LPS) led to its induction in cultured neonatal myocytes. LPS also activated the NF-kappaB pathway, as evidenced by the degradation of the inhibitory protein IkappaB and the appearance of NF-kappaB-binding complexes in nuclear extracts. Furthermore, inhibitors of NF-kappaB activation, such as lactacystin, MG132, and pyrrolidine dithiocarbamate, were found to completely block the production of TNF-alpha in response to LPS stimulation, indicating a requirement of NF-kappaB for TNF-alpha expression. However, interleukin-1beta and phorbol 12-myristate 13-acetate also activated NF-kappaB but did not evoke TNF-alpha expression, revealing that this factor is not sufficient for cytokine production. Detailed examination of the NF-kappaB cascade revealed that cardiac cells displayed a unique pattern of IkappaB degradation in response to LPS, with IkappaBbeta but not IkappaBalpha being degraded upon stimulation. Additionally, two specific p65-containing DNA-binding complexes were observed in the nuclear extracts of neonatal cardiomyocytes: an inducible complex that is necessary for TNF-alpha expression and a constitutive species. Taken together, these results reveal that NF-kappaB is not only involved in cytokine production but also may be linked to other pathways that subserve a constitutive, protective mechanism for the heart cell. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|