Abstract | BACKGROUND: METHODS: RESULTS:
Caspase-3 and caspase-7 activity was more than 100% increased in homozygous (Cy/Cy) compared to heterozygous (Cy/+) and normal littermate control (+/+) kidneys. Ribonuclease protection assays demonstrated no difference in caspase-3 mRNA. On immunoblotting, there was an increase in the proform of caspase-3 and caspase-7 in Cy/Cy compared to +/+ and Cy/+ kidneys. Caspase-8 and caspase-9 activity was more than 100% increased in Cy/Cy compared to Cy/+ and +/+ kidneys. On immunoblotting, there was an increase of the proform of both caspase-8 and caspase-9 in Cy/Cy kidneys. There was also an increase in cytochrome c release into the cytosol and an increase in caspase-2 protein and activity in Cy/Cy kidneys. On ribonuclease protection assay there was no difference in FasL mRNA between +/+, Cy/+, and Cy/Cy kidneys. Short-term treatment of Cy/Cy rats with the caspase inhibitor IDN-8050 resulted in inhibition of caspase-3 and caspase-7 activity in the kidney. CONCLUSION: In Cy/Cy kidneys with ADPKD, there was an increase of the proform of caspase-9, an increase in cytochrome c release into the cytosol, and an increase in caspase-2 protein and activity demonstrating involvement of the intrinsic pathway. There was an increase in the proform of caspase-8 demonstrating involvement of the extrinsic pathway. No differences in FasL mRNA were seen suggesting that the extrinsic pathway is independent of the death receptor ligand, FasL.
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Authors | Yunxia Tao, Jun Kim, Melinda Stanley, Zhibin He, Sarah Faubel, Robert W Schrier, Charles L Edelstein |
Journal | Kidney international
(Kidney Int)
Vol. 67
Issue 3
Pg. 909-19
(Mar 2005)
ISSN: 0085-2538 [Print] United States |
PMID | 15698430
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Amino Acid Chloromethyl Ketones
- Fas Ligand Protein
- Faslg protein, rat
- Membrane Glycoproteins
- RNA, Messenger
- benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
- Casp3 protein, rat
- Casp8 protein, rat
- Caspase 3
- Caspase 7
- Caspase 8
- Caspases
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Topics |
- Amino Acid Chloromethyl Ketones
(pharmacology)
- Animals
- Apoptosis
- Caspase 3
- Caspase 7
- Caspase 8
- Caspases
(physiology)
- Fas Ligand Protein
- Immunohistochemistry
- Membrane Glycoproteins
(genetics)
- Polycystic Kidney, Autosomal Dominant
(pathology, physiopathology)
- RNA, Messenger
(analysis)
- Rats
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