Abstract
Recent studies have suggested that carbon monoxide (CO) inhalation can reduce ischemia-reperfusion injury of kidneys. The purpose of the present study was to determine whether the direct application of CO using tricarbonylchloro (glycinato) ruthenium II (CORM3) would reduce cold-rewarm-associated apoptosis in renal tubular epithelial (RPTE) cells. RPTE cells were subjected to 48 hours of cold followed by 24 hours of rewarming with increasing concentrations (0-500 μM) of CORM3. CORM3 (100 μM) reduced apoptosis as determined by the TUNEL method from 21.6 ± 5.2 to 5.8 ± 1.1 % (untreated vs. treated, n = 5; p < 0.001). We subsequently observed that the incubation of RPTE cells with CORM3 induced heme oxygenase (HO)-1 gene expression. As HO-1 itself can confer protection against cold rewarm injury, we investigated the role of HO-1 in the protective actions of CORM3 using siRNA oligonucleotides directed against HO-1. CORM3 treatment of RPTE cells caused a 4.9- fold increase in HO-1 gene expression as determined by real time PCR. Prior treatment of RPTE cells with siRNAs against HO-1 was able to completely abolish the CORM3 mediated induction of HO-1 mRNA and protein. The abolition of HO-induction with siRNAs did reduce CORM3-mediated protection against cold rewarm-induced apoptosis; however, CORM3 was able to significantly protect RPTE cells against cold-rewarm injury: apoptosis was 33.7 ± 0.9% vs. 15.4 ± 0.5% vs. 62.8 ± 1.5% vs. 23.5 ± 3.4 in control cold-rewarm vs. cold-rewarm + CORM3 (100 μM) vs. cold-rewarm + HO-1 siRNA vs. cold-rewarm + CORM3 (100 μM) + HO-1 siRNA (n = 4). These results suggest that increased levels of CO alone can protect against cold-rewarm-induced apoptosis.
Original language | English (US) |
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Pages (from-to) | 543-548 |
Number of pages | 6 |
Journal | Renal Failure |
Volume | 29 |
Issue number | 5 |
DOIs | |
State | Published - Jun 2007 |
Keywords
- Apoptosis
- Carbon monoxide
- Cold-rewarm injury
- Heme oxygenase
- Renal tubular epithelial cells
ASJC Scopus subject areas
- Critical Care and Intensive Care Medicine
- Nephrology