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Articles in PresS, published online ahead of print February 12, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00317.2001
Submitted on October 23, 2001
Accepted on February 6, 2002
1 Department of Internal Medicine III, Division of Nephrology and Dialysis, University of Vienna, Vienna, Austria
2 Institute for Theoretical Chemistry and Molecular Structural Biology, University of Vienna, Vienna, Austria
3 Institute of Pharmacology, University of Vienna, Vienna, Austria
4 Division of Nephrology and Dialysis, University of Innsbruck, Innsbruck, Austria
* To whom correspondence should be addressed. E-mail: rainer.oberbauer{at}akh-wien.ac.at.
Bcl-2 protein family members are among the key regulators of the apoptosis effector phase. Therefore, we investigated the ability of synthetic peptides derived from proteins of the Bcl-2 family, namely the N-terminal region of Bcl-2 (Bcl2_syn), a central domain of Bax (Bax_syn), as well as central domain of Bak (Bak_syn) to interfere with the apoptotic process in LLC-PK1 cells. Apoptosis was induced by tacrolimus or LPS treatment, and microinjection of Bcl2_syn into stimulated LLC-PK1 cells significantly reduced the percentage of apoptotic cells detected within four hours after the treatment. Microinjection of Bax_syn or Bax_syn, in contrast, induced apoptosis in otherwise untreated LLC-PK1 cells during the same period of time. A random sequence control peptide (control_syn), which served as a negative control, as well as FITC-labeled dextran, which was co-injected in all experiments for visualization, were ineffective in either preventing or inducing apoptosis. These results suggest that synthetic peptides mimicking the functional domains of proteins of the Bcl-2 family are capable of regulating apoptosis when microinjected into LLC-PK1 cells in vivo. Analoga to these regulatory peptides could therefore provide valuable lead compounds in the therapeutical context.
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