Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Kim, RD; Darling, CE; Cerwenka, H; Chari, RS.
Hypoosmotic stress activates p38, ERK 1 and 2, and SAPK/JNK in rat hepatocytes.
J SURG RES 2000 90: 58-66.
Doi: 10.1006/jsre.2000.5866
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Cerwenka Herwig
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- Abstract:
- BACKGROUND: Following hepatocyte injury, changes in the perihepatocyte milieu modulate cell volume and influence growth. Hypoosmotic stress activates nuclear factor-kappa B (NF-kappaB), a transcription factor believed to prime cell cycle progression in hepatocytes. In this study, we investigate the role of mitogen-activated protein kinases (MAPKs) in the activation of NF-kappaB. MATERIALS AND METHODS: Quiescent primary hepatocytes were exposed to hypoosmotic serum-free William's E (WE) medium (200 mOsm/liter), with or without a 1-h pretreatment with either PD 98059 (15 microM) or SB 202190 (3 microM). Parallel experiments were conducted using hepatocyte growth factor (HGF) at 0.1 mg/ml and normoosmotic WE medium as positive and negative controls, respectively (n = 3). Relative densitometries of Western blots measured phosphorylated cytoplasmic p38, ERK 1 and 2, and SAPK/JNK. Electromobility shift assays examined nuclear NF-kappaB activation. RESULTS: (i) Hypoosmolar WE medium phosphorylated p38, ERK 1 and 2, and SAPK/JNK by 5 min. (ii) Hypoosmolar WE medium activated NF-kappaB at 60 min. (iii) HGF phosphorylated all three MAPKs and activated NF-kappaB with profiles similar to those of hypoosmotic stress. (iv) Both PD 98059 and SB 202190 abrogated the activation of NF-kappaB in HGF-stimulated cells but not in hypoosmotically stressed cells. CONCLUSION: (i) Both hypoosmotic cell swelling and HGF phosphorylate p38, ERK 1 and 2, and SAPK/JNK, and (ii) HGF, but not hypoosmotic stress, activates NF-kappaB via p38 and ERK 1 and 2 phosphorylation. These data suggest that cell swelling activates NF-kappaB through a pathway separate from that of growth factors.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Hepatocyte Growth Factor - pharmacology
- Hypotonic Solutions - pharmacology
- Liver - cytology
- Male - cytology
- Mitogen-Activated Protein Kinase 1 - physiology
- Mitogen-Activated Protein Kinase 3 - physiology
- Mitogen-Activated Protein Kinase 8 - physiology
- Mitogen-Activated Protein Kinases - physiology
- NF-kappa B - physiology
- Phosphorylation - physiology
- Rats - physiology
- Rats, Sprague-Dawley - physiology
- p38 Mitogen-Activated Protein Kinases - physiology
- Find related publications in this database (Keywords)
- MAPK
- NF-kappa B
- hypoosmotic