geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

P53 mediates the apoptotic response to GTP depletion after renal ischemia-reperfusion: protective role of a p53 inhibitor


, : P53 mediates the apoptotic response to GTP depletion after renal ischemia-reperfusion: protective role of a p53 inhibitor. Journal of the American Society of Nephrology 14(1): 128-138

Ischemic injury to the kidney is characterized in part by nucleotide depletion and tubular cell death in the form of necrosis or apoptosis. GTP depletion was recently identified as an important inducer of apoptosis during chemical anoxia in vitro and ischemic injury in vivo. It has also been shown that GTP salvage with guanosine prevented apoptosis and protected function. This study investigates the role of p53 in mediating the apoptotic response to GTP depletion. Male Sprague-Dawley rats underwent bilateral renal artery clamp for 30 min followed by reperfusion. p53 protein levels increased significantly in the medulla over 24 h post-ischemia. The provision of guanosine inhibited the increase in p53. Pifithrin-alpha, a specific inhibitor of p53, mimicked the effects of guanosine. It had no effect on necrosis, yet it prevented apoptosis and protected renal function. Pifithrin-alpha was protective when given up to 14 h after the ischemic insult. The effects of pifithrin-alpha on p53 included inhibition of transcriptional activation of downstream p53 targets like p21 and Bax and inhibition of p53 translocation to the mitochondria. Similar results were obtained in cultured renal tubular cells. It is concluded that p53 is an important mediator of apoptosis during states of GTP depletion. Inhibitors of p53 should be considered in the treatment of ischemic renal injury.

US$19.90

PMID: 12506145

DOI: 10.1097/01.asn.0000040596.23073.01


Other references

Roy, R.C.; Grohs, R.; Reeleder, R.D., 2003: A method for the classification by shape of dried roots of ginseng (Panax quinquefolius L.). A system for classifying the dried roots of ginseng by shape was developed using roots from 3- and 4-year-old plantings. The method is based on traditional preferences in the marketplace and allows for the separation of desirable roots (chunk or f...

Hepher B.; Milstein A.; Leventer H.; Teltsch B., 1989: The effect of fish density and species combination on growth and utilization of natural food in ponds. Interactions between bottom-feeding fish (common carp, Cyprinus carpio L., and hybrid tilapia) and a filter feeder (silver carp, Hypophthalmichthys molitrix (Valenciennes)) in polyculture were studied in fertilized ponds with no supplementary feed...

Pratt R., 1980: Iron and steel (including ferroalloys). Australian Mineral Industry Annual Review 1978: 134-139

Nagy, I.; Ohno-Iwashita, Y.; Ohta, M.; Nagy, V.; Kitani, K.; Ando, S.; Imahori, K., 1988: Effect of perfringolysin O on the lateral diffusion constant of membrane proteins of hepatocytes as revealed by fluorescence recovery after photobleaching. Perfringolysin O is a thiol-activated cytolytic exotoxin the primary receptor of which is the membrane cholesterol on the cell surface. The effect of perfringolysin O was tested in various hepatocyte preparations. (i) Smears of fresh liver exposed...

von Ilberg, C.; Arnold, W., 1971: Localisation and frequency of laryngeal carcinoma recidivations. Archiv für Klinische und Experimentelle Ohren- Nasen- und Kehlkopfheilkunde 199(2): 719-724

Yi, E.S.; Powell, H.C., 1994: Adenovirus infection of the duodenum in an AIDS patient: an ultrastructural study. Intractable diarrhea in a 40-year-old woman with terminal acquired immunodeficiency syndrome resulted from adenovirus infection of the duodenal mucosa. Electron microscopic examination of a duodenal biopsy specimen performed because of clinical su...

Perlich, M.A.; Reader, A.; Foreman, D.W., 1981: A scanning electron microscopic investigation of accessory foramens on the pulpal floor of human molars. Journal of Endodontics 7(9): 402-406

Knoblauch, K.; D'Zmura, M., 2001: Reply to letter to editor by M.J. Sankeralli and K.T. Mullen published in Vision Research, 41, 53-55: Lights and neural responses do not depend on choice of color space. Vision Research 41(13): 1683-1684

Tveito, K., 2016: Not Available. Tidsskrift for den Norske Laegeforening 136(17): 1438-1441

Cunha-Cruz, J.; Wataha, J.C.; Zhou, L.; Manning, W.; Trantow, M.; Bettendorf, M.M.; Heaton, L.J.; Berg, J., 2010: Treating dentin hypersensitivity: therapeutic choices made by dentists of the northwest PRECEDENT network. Methods used by dental practitioners to diagnose and treat dentin hypersensitivity are not well documented. The authors conducted a survey of dentists in the Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry (PRECEDENT) t...