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Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes
15:43

Assessment of Mitochondrial Functions and Cell Viability in Renal Cells Overexpressing Protein Kinase C Isozymes

Published on: January 7, 2013

Renal tubule necrosis and apoptosis modulation by A1 adenosine receptor expression

H T Lee1, M Kim, M Jan

  • 1Department of Anesthesiology, College of Physicians and Surgeons of Columbia University, New York, New York 10032-3784, USA. tl128@columbia.edu

Kidney International
|April 13, 2007
PubMed

Insights

A1 adenosine receptors protect kidney cells from damage and death. Activating these receptors increases heat-shock protein 27, a key factor in cell survival.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Biology

Background:

  • A1 adenosine receptors (A1ARs) are known to be cytoprotective against renal tubular necrosis and apoptosis.
  • Understanding the role of A1AR expression levels in renal epithelial cell survival is crucial for developing protective strategies.

Purpose of the Study:

  • To investigate the impact of A1AR numbers on renal epithelial cell survival.
  • To elucidate the signaling pathways involved in A1AR-mediated cytoprotection.

Main Methods:

  • Stable overexpression of human A1AR in a porcine renal tubule cell line.
  • Primary cultures of proximal tubules from A1AR knockout mice.
  • Assessment of cell death (necrosis and apoptosis) and heat-shock protein (HSP)27 expression and phosphorylation.
  • Evaluation of mitogen-activated protein kinase (MAPK) activities (p38 and AP2).

Main Results:

  • Receptor-overexpressing cells showed protection against peroxide-induced necrosis and TNF-α/CHX-induced apoptosis.
  • A1AR knockout mouse cells exhibited increased necrotic and apoptotic cell loss compared to wild-type.
  • A1AR overexpression elevated baseline total and phosphorylated HSP27, mediated by p38 and AP2 MAPK.
  • Cytoprotection was reversed by A1AR antagonism and HSP synthesis inhibition.
  • In vivo, A1AR activation increased HSP27 phosphorylation, while knockout mice showed reduced phosphorylation.

Conclusions:

  • Endogenous A1AR activation confers cytoprotective effects in renal proximal tubules.
  • A1ARs modulate HSP27 signaling pathways, contributing to renal cell survival.
  • A1ARs represent a potential therapeutic target for preventing kidney injury.

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