p38 MAPK mediates renal tubular cell TNF-α production and TNF-α-dependent apoptosis during simulated ischemia

K. K. Meldrum, D. R. Meldrum, K. L. Hile, E. B. Yerkes, A. Ayala, M. P. Cain, R. C. Rink, Anthony J. Casale, M. A. Kaefer

Research output: Contribution to journalArticle

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Abstract

Ischemia causes renal tubular cell loss through apoptosis; however, the mechanisms of this process remain unclear. Using the renal tubular epithelial cell line LLC-PK1, we developed a model of simulated ischemia (SI) to investigate the role of p38 MAPK (mitogen-activated protein kinase) in renal cell tumor necrosis factor-α (TNF-α) mRNA production, protein bioactivity, and apoptosis. Results demonstrate that 60 min of SI induced maximal TNF-α mRNA production and bioactivity. Furthermore, 60 min of ischemia induced renal tubular cell apoptosis at all substrate replacement time points examined, with peak apoptotic cell death occurring after either 24 or 48 h. p38 MAPK inhibition abolished TNF-α mRNA production and TNF-α bioactivity, and both p38 MAPK inhibition and TNF-α neutralization (anti-porcine TNF-α antibody) prevented apoptosis after 60 min of SI. These results constitute the initial demonstration that 1) renal tubular cells produce TNF-α mRNA and biologically active TNF-α and undergo apoptosis in response to SI, and 2) p38 MAPK mediates renal tubular cell TNF-α production and TNF-α-dependent apoptosis after SI.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume281
Issue number2 50-2
StatePublished - 2001
Externally publishedYes

Fingerprint

p38 Mitogen-Activated Protein Kinases
Ischemia
Tumor Necrosis Factor-alpha
Apoptosis
Kidney
Bioactivity
Messenger RNA
Cell death
Cell Death
Demonstrations
Swine
Epithelial Cells
Cell Line
Antibodies

Keywords

  • Cytokine
  • Inflammation
  • Necrosis

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Meldrum, K. K., Meldrum, D. R., Hile, K. L., Yerkes, E. B., Ayala, A., Cain, M. P., ... Kaefer, M. A. (2001). p38 MAPK mediates renal tubular cell TNF-α production and TNF-α-dependent apoptosis during simulated ischemia. American Journal of Physiology - Cell Physiology, 281(2 50-2).

p38 MAPK mediates renal tubular cell TNF-α production and TNF-α-dependent apoptosis during simulated ischemia. / Meldrum, K. K.; Meldrum, D. R.; Hile, K. L.; Yerkes, E. B.; Ayala, A.; Cain, M. P.; Rink, R. C.; Casale, Anthony J.; Kaefer, M. A.

In: American Journal of Physiology - Cell Physiology, Vol. 281, No. 2 50-2, 2001.

Research output: Contribution to journalArticle

Meldrum, KK, Meldrum, DR, Hile, KL, Yerkes, EB, Ayala, A, Cain, MP, Rink, RC, Casale, AJ & Kaefer, MA 2001, 'p38 MAPK mediates renal tubular cell TNF-α production and TNF-α-dependent apoptosis during simulated ischemia', American Journal of Physiology - Cell Physiology, vol. 281, no. 2 50-2.
Meldrum, K. K. ; Meldrum, D. R. ; Hile, K. L. ; Yerkes, E. B. ; Ayala, A. ; Cain, M. P. ; Rink, R. C. ; Casale, Anthony J. ; Kaefer, M. A. / p38 MAPK mediates renal tubular cell TNF-α production and TNF-α-dependent apoptosis during simulated ischemia. In: American Journal of Physiology - Cell Physiology. 2001 ; Vol. 281, No. 2 50-2.
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AU - Yerkes, E. B.

AU - Ayala, A.

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