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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Tumor necrosis factor-alpha induces intrinsic apoptotic signaling during renal obstruction through truncated bid

Matthew T Campbell1, Pierre Dagher, Karen L Hile

  • 1Department of Urology, Riley Hospital for Children, Indianapolis, Indiana 46202, USA.

The Journal of Urology
|October 28, 2008
PubMed
Abstract

Insights

Tumor necrosis factor-alpha (TNF-α) drives kidney injury during ureteral obstruction by activating intrinsic apoptosis. Neutralizing TNF-α with a soluble receptor treatment reduced apoptosis and protected kidney function.

Area of Science:

  • Nephrology
  • Cell Biology
  • Immunology

Background:

  • Renal tubular cell apoptosis is a key feature of obstruction-induced renal injury.
  • Tumor necrosis factor-alpha (TNF-α) is implicated in extrinsic apoptotic pathways during renal obstruction.
  • The role of TNF-α in intrinsic apoptotic signaling and mitochondrial cytochrome C release during renal obstruction remains unevaluated.

Purpose of the Study:

  • To investigate the effect of TNF-α on intrinsic apoptotic signaling and mitochondrial cytochrome C release in obstruction-induced renal injury.
  • To evaluate the therapeutic potential of TNF-α neutralization in this injury model.

Main Methods:

  • Male Sprague-Dawley rats underwent unilateral ureteral obstruction or sham surgery.
  • Animals received vehicle or pegylated soluble TNF receptor type 1 (p TNFR1).
  • Kidney tissues were analyzed for TNF-α, apoptosis markers, Bcl-2 family proteins, caspase 8, truncated Bid, and mitochondrial cytochrome C release.

Main Results:

  • Renal obstruction increased TNF-α production, apoptosis, Bax, caspase 8, truncated Bid, and mitochondrial cytochrome C release, while decreasing Bcl-2 and Bcl-x(L).
  • p TNFR1 treatment significantly reduced these obstruction-induced changes.
  • p TNFR1 treatment also increased Bcl-2 and Bcl-x(L) expression.

Conclusions:

  • TNF-α activates Bid and the intrinsic apoptotic pathway during ureteral obstruction, leading to mitochondrial cytochrome C release and cell death.
  • TNF-α neutralization is a potential therapeutic strategy for obstruction-induced renal injury.

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