Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Hochegger, K; Koppelstaetter, C; Tagwerker, A; Huber, JM; Heininger, D; Mayer, G; Rosenkranz, AR.
p21 and mTERT are novel markers for determining different ischemic time periods in renal ischemia-reperfusion injury.
Am J Physiol Renal Physiol. 2007; 292(2):F762-F768
Doi: 10.1152/ajprenal.00084.2006
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- Führende Autor*innen der Med Uni Graz
- Eller Kathrin
- Rosenkranz Alexander
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- Abstract:
- In many clinical settings, the duration of renal ischemia and therefore the outcome of acute renal failure cannot be determined adequately. Renal ischemia reperfusion injury is known to shorten telomeres and upregulate stress-induced genes, such as the cyclin-dependent kinase (CDK) inhibitor p21. So far, the expression and role of CDK inhibitors, as well as mouse telomerase reverse transcriptase (mTERT), has not been investigated in a model with variable lasting ischemic periods. Male C57Bl/6 mice were subjected to renal ischemia reperfusion injury by clamping both renal pedicles for 10, 20, 30, and 45 min, and the kidneys were allowed to be reperfused for 3, 24, and 48 h. Expression of different CDK inhibitors and mTERT was evaluated. Mice developed signs of acute renal failure linear to the duration of the ischemic period. Real-time PCR revealed that mTERT was only significantly upregulated in kidneys after short ischemic periods (20 min). In contrast, p21 was constantly upregulated in kidneys after long ischemic intervals (30 and 45 min), but not in kidneys, which were clamped for shorter periods. Mainly, tubular cells contributed to the observed increase in p21 expression. Targeting p21 via the selective p53 inhibitor pifithrin-alpha was able to prevent acute renal failure when administered immediately before ischemia. The expression of another CDK inhibitor, namely p16, was differentially regulated, depending on the time of reperfusion. Taken together, we detected mTERT and p21 as "indicator" genes for short and long ischemic intervals, respectively. These two proteins might also be possible new therapeutic targets in the treatment and prevention of acute renal failure.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Benzothiazoles - pharmacology
- Biological Markers - analysis
- Cyclin-Dependent Kinase Inhibitor p16 - biosynthesis
- Cyclin-Dependent Kinase Inhibitor p21 - analysis Cyclin-Dependent Kinase Inhibitor p21 - biosynthesis Cyclin-Dependent Kinase Inhibitor p21 - physiology
- Ischemia - diagnosis
- Kidney Diseases - diagnosis Kidney Diseases - etiology Kidney Diseases - physiopathology
- Male -
- Mice -
- Mice, Inbred C57BL -
- Reperfusion Injury - diagnosis Reperfusion Injury - prevention and control
- Telomerase - analysis Telomerase - biosynthesis
- Time -
- Toluene - analogs and derivatives Toluene - pharmacology
- Find related publications in this database (Keywords)
- cyclin-dependent kinase inhibitors
- acute renal failure
- cell cycle