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Regulation of tumor necrosis factor cytotoxicity by calcineurin.

Publication ,  Journal Article
Kantrow, SP; Gierman, JL; Jaligam, VR; Zhang, P; Piantadosi, CA; Summer, WR; Lancaster, JR
Published in: FEBS Lett
October 20, 2000

Cyclosporin (CsA) inhibits mitochondrial death signaling and opposes tumor necrosis factor (TNF)-induced apoptosis in vitro. However, CsA is also a potent inhibitor of calcineurin, a phosphatase that may participate in cell death. Therefore, we tested the hypothesis that calcineurin regulates TNF cytotoxicity in rat hepatoma cells (FTO2B). TNF-treated FTO2B cells appeared apoptotic by DNA fragmentation, nuclear condensation, annexin V binding, and caspase activation. We studied two calcineurin inhibitors, CsA and FK506, and found that each potently inhibited TNF cytotoxicity. Western blot demonstrated calcineurin in FTO2B homogenates. In a model of mitochondrial permeability transition (MPT), we found that CsA prevented MPT and cytochrome c release, while FK506 inhibited neither. In summary, we present evidence that calcineurin participates in an apoptotic death pathway activated by TNF. CsA may oppose programmed cell death by inhibiting calcineurin activity and/or inhibiting mitochondrial signaling.

Duke Scholars

Published In

FEBS Lett

DOI

ISSN

0014-5793

Publication Date

October 20, 2000

Volume

483

Issue

2-3

Start / End Page

119 / 124

Location

England

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tumor Cells, Cultured
  • Tacrolimus
  • Rats, Sprague-Dawley
  • Rats
  • Permeability
  • Mitochondrial Swelling
  • Mitochondria, Liver
  • L-Lactate Dehydrogenase
  • Intracellular Membranes
 

Citation

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Kantrow, S. P., Gierman, J. L., Jaligam, V. R., Zhang, P., Piantadosi, C. A., Summer, W. R., & Lancaster, J. R. (2000). Regulation of tumor necrosis factor cytotoxicity by calcineurin. FEBS Lett, 483(2–3), 119–124. https://doi.org/10.1016/s0014-5793(00)02083-4
Kantrow, S. P., J. L. Gierman, V. R. Jaligam, P. Zhang, C. A. Piantadosi, W. R. Summer, and J. R. Lancaster. “Regulation of tumor necrosis factor cytotoxicity by calcineurin.FEBS Lett 483, no. 2–3 (October 20, 2000): 119–24. https://doi.org/10.1016/s0014-5793(00)02083-4.
Kantrow SP, Gierman JL, Jaligam VR, Zhang P, Piantadosi CA, Summer WR, et al. Regulation of tumor necrosis factor cytotoxicity by calcineurin. FEBS Lett. 2000 Oct 20;483(2–3):119–24.
Kantrow, S. P., et al. “Regulation of tumor necrosis factor cytotoxicity by calcineurin.FEBS Lett, vol. 483, no. 2–3, Oct. 2000, pp. 119–24. Pubmed, doi:10.1016/s0014-5793(00)02083-4.
Kantrow SP, Gierman JL, Jaligam VR, Zhang P, Piantadosi CA, Summer WR, Lancaster JR. Regulation of tumor necrosis factor cytotoxicity by calcineurin. FEBS Lett. 2000 Oct 20;483(2–3):119–124.
Journal cover image

Published In

FEBS Lett

DOI

ISSN

0014-5793

Publication Date

October 20, 2000

Volume

483

Issue

2-3

Start / End Page

119 / 124

Location

England

Related Subject Headings

  • Tumor Necrosis Factor-alpha
  • Tumor Cells, Cultured
  • Tacrolimus
  • Rats, Sprague-Dawley
  • Rats
  • Permeability
  • Mitochondrial Swelling
  • Mitochondria, Liver
  • L-Lactate Dehydrogenase
  • Intracellular Membranes