Cited by 249Cell death mechanisms and regulationProtein Tyrosine PhosphatasesNF-κB Signaling Pathways

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Correlation between Sustained c-Jun N-terminal Protein Kinase Activation and Apoptosis Induced by Tumor Necrosis Factor-α in Rat Mesangial Cells

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Guo, Yan-Lin, Baysal, Kemal, Kang, Baobin, Yang, Li-Jun, Williamson, John R.·1998·Journal of Biological Chemistry

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Abstract

Rat mesangial cells are normally resistant to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis. In this report we show that the cells can be made susceptible to the apoptotic effect of TNF-alpha when pretreated with actinomycin D, cycloheximide, or vanadate. c-Jun N-terminal protein kinase (JNK) has been thought to mediate apoptotic processes elicited by some stimuli, but its involvement in TNF-alpha-induced apoptosis has been controversial. JNK activation was investigated under conditions where the mesangial cells were either resistant or susceptible to TNF-alpha-induced apoptosis. TNF-alpha alone stimulated a single transient JNK activity peak. However, when the cells were pretreated with actinomycin D or cycloheximide, TNF-alpha stimulated a second sustained JNK activity peak. When the cells were pretreated with the phosphatase inhibitor vanadate, TNF-alpha-induced JNK activation was greatly prolonged. In all three cases, a sustained JNK activation was associated with the initiation of apoptosis. Our data suggest that a sustained activation of JNK induced by these reagents may be associated with blocking the expression of a phosphatase that inactivates JNK. Further studies reveal that the expression of mitogen-activated protein kinase phosphatase-1 (MKP-1) was induced by TNF-alpha, indicating that MKP-1 may be involved in protecting the cells from apoptosis by preventing a prolonged activation of JNK under normal conditions. Additional studies showed that extracellular signal-regulated protein kinase activation stimulated by TNF-alpha was unlikely to contribute to the resistance of mesangial cells to TNF-alpha cytotoxicity.

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Authors: Guo, Y.-L., Baysal, K., Kang, B., Yang, L.-J., & Williamson, J. R.
Affiliations: University of Pennsylvania (US)
Corresponding author: Williamson, John R.
ORCID: Guo, Yan-Lin
Baysal, Kemal
Venue: Journal of Biological Chemistry
Publisher: Elsevier BV
Published: 1998-02
Volume: 273
Issue: 7
Pages: 4027-4034
ISSN: 0021-9258 (ISSN-L)
DOI: 10.1074/jbc.273.7.4027
OpenAlex: W1993170284
Cited by: 249
References: 51
Citations by year: 2023: 2 · 2022: 1 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 3 · 2014: 6 · 2013: 7 · 2012: 8
FWCI: 10.26
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 8309 d)
Locations: Journal of Biological Chemistry (publishedVersion, cc-by)
PubMed (publishedVersion)
Funders: American Diabetes Association
National Institutes of Health (5r01dk048493-04, 5r01dk015120-25)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 15120, DK-48493, DK-07314)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords: JNK activation, TNF-α, apoptosis, mesangial cells, MKP-1, protein phosphatase, actinomycin D, cycloheximide, vanadate, ERK activation, apoptosis resistance
MeSH terms: Animals, Cell Survival, Cells, Cultured, Cycloheximide, Dactinomycin, Enzyme Activation, Glomerular Mesangium, Phosphoprotein Phosphatases, Tumor Necrosis Factor-alpha, Vanadates, NF-kappa B, Protein Tyrosine Phosphatases, Rats, Sprague-Dawley, Apoptosis, Calcium-Calmodulin-Dependent Protein Kinases, Immediate-Early Proteins, Cell Cycle Proteins, Okadaic Acid, Mitogen-Activated Protein Kinase 1, Mitogen-Activated Protein Kinases, JNK Mitogen-Activated Protein Kinases, Rats, Dual Specificity Phosphatase 1, Protein Phosphatase 1

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Correlation between Sustained c-Jun N-terminal Protein Kinase Activation and Apoptosis Induced by Tumor Necrosis Factor-α in Rat Mesangial Cells

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