Bilirubin, a curse and a boon
| Autor: | J. D. Ostrow, Claudio Tiribelli |
|---|---|
| Přispěvatelé: | Ostrow, Jd, Tiribelli, Claudio |
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Programmed cell death
Bilirubin Apoptosis Fatty Acid-Binding Proteins ATP-Binding Cassette Transporters/metabolism Bilirubin/physiology* Carrier Proteins/metabolism Fatty Acid-Binding Proteins Hepatocytes/metabolism Humans Hyperbilirubinemia/complications* Oxidation-Reduction Tumor Suppressor Proteins Bile Acids and Salts chemistry.chemical_compound Cholestasis medicine Humans Animals Bovine serum albumin Hyperbilirubinemia biology Dose-Response Relationship Drug Tumor Suppressor Proteins Gastroenterology Albumin medicine.disease Ursodeoxycholic acid Enzymes Rats chemistry Biochemistry Liver Toxicity biology.protein Commentary Hepatocytes ATP-Binding Cassette Transporters Carrier Proteins Fatty Acid-Binding Protein 7 Reactive Oxygen Species Oxidation-Reduction medicine.drug |
| Popis: | Unconjugated bilirubin is a curse at high concentrations, producing apoptosis and cell death, but a boon at more physiological levels, protecting cells against oxidant damage Both hydrophobic bile salts1,2 and unconjugated bilirubin (UCB)3 induce apoptosis in cultured cells at moderately elevated concentrations and cell necrosis at higher concentrations. Retention of bile salts in cholestasis is believed to cause secondary damage to hepatocytes,4 and retention of UCB in severe neonatal jaundice is known to cause bilirubin encephalopathy.5 For both agents, the cytotoxicity results from damage to mitochondrial membranes, with collapse of the transmembrane potential and generation of a mitochondrial membrane permeability transition,1–2,6 and ursodeoxycholic acid or its amidates can prevent apoptosis by inhibiting this process.1–2,7 It is therefore surprising that, as reported by Granato et al in this issue of Gut ,8 UCB, at concentrations far above those known to be cytotoxic to neurones and astrocytes,3 is protective against apoptosis induced in cultured rat hepatocytes by the hydrophobic bile salt glycochenodeoxycholate (GCDC) [see page 1774] . This finding raises interesting questions concerning whether UCB is a curse or a boon, and why various organs and tissues have such different susceptibilities to toxicity from these substances. Like many previous in vitro studies of the cytotoxicity of UCB9 and bile salts,10 the studies of Granato and colleagues8 were performed at concentrations of the unbound fraction far above those that are clinically relevant. Although the incubation media contained 18 µM bovine serum albumin, concentrations of UCB and GCDC greatly exceeded the high affinity binding capacity of 1 mol/mol albumin. The final unbound concentrations of UCB (Bf) were also far above aqueous saturation,11 so the pigment must have been heavily self aggregated.12,13 Unbound concentrations … |
| Databáze: | OpenAIRE |
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