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Cyclosporin treatment alters protein phosphorylation in kidney membranes

M Demeule1, S Giroux, G F Murphy

  • 1Département de chimie-biochimie, Université du Québec à Montréal, Canada.

Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire
|March 1, 1994
PubMed

Insights

Cyclosporin A (CsA) treatment alters kidney signal transduction by increasing protein phosphorylation in renal membranes and cytosol. These changes involve protein kinase C and tyrosine protein kinase activities in basolateral membranes.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Biochemistry

Background:

  • Cyclosporin A (CsA) is an immunosuppressant with known nephrotoxic effects.
  • Signal transduction pathways in kidney cells are crucial for maintaining renal function.
  • Understanding CsA's impact on these pathways is vital for managing its side effects.

Purpose of the Study:

  • To investigate the effects of CsA on signal transduction mechanisms in rat kidney cortex.
  • To specifically examine alterations in protein phosphorylation, methylation, and ADP-ribosylation.
  • To assess changes in protein kinase activities following CsA administration.

Main Methods:

  • Isolated renal basolateral and brush border membranes and cytosolic fractions from rats treated with CsA.
  • Assayed protein phosphorylation, protein carboxyl methylation, and ADP-ribosylation.
  • Determined activities of protein kinase A, protein kinase C, and tyrosine protein kinase.

Main Results:

  • CsA treatment significantly increased the phosphorylation of specific endogenous substrates in both brush border and basolateral membranes.
  • Cytosolic protein phosphorylation also showed significant increases and decreases in specific proteins.
  • Protein kinase C and tyrosine protein kinase activities were elevated in basolateral membranes, with CsA stimulating tyrosine kinase substrates.

Conclusions:

  • Cyclosporin A administration alters protein phosphorylation patterns in rat kidney cortex membranes and cytosol.
  • Increased protein kinase C and tyrosine protein kinase activities in basolateral membranes suggest a role in CsA-induced renal effects.
  • These findings highlight potential mechanisms of CsA nephrotoxicity related to signal transduction pathway dysregulation.

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