title: Mechanism of intracellular signal transduction during injury of renal tubular cells induced by postasphyxial serum in neonates with asphyxia.
abstract: BACKGROUND
  Renal injury is a severe and extremely common complication that occurs early in neonates with asphyxia. Reperfusion injury has been suggested as the cause of kidney damage during resuscitation of neonatal asphyxia. Previous studies have demonstrated that postasphyxial serum from neonates with asphyxia may result in apoptosis of renal tubular cells. However, the mechanisms that mediate renal tubular cell apoptosis induced by postasphyxial serum remain poorly understood.
  
  
  OBJECTIVE
  In this report we investigate the intracellular signal transduction mechanisms that operate during injury of renal tubular cells induced by postasphyxial serum in neonates.
  
  
  METHODS
  Cultured human renal proximal tubular cells HK-2 cell were exposed to 10% fetal calf serum (normal control), 20% postasphyxial serum or 20% postasphyxial serum with pyrrolidine dithiocarbamate (PDTC). The expression of both BAD and BAX in the cytoplasm was detected by immunohistochemistry. The mitochondria membrane potential (Deltapsim) was examined by confocal microscopy, and the release of the apoptogenic mitochondrial proteins cytochrome C and AIF was assessed by Western blot analysis.
  
  
  RESULTS
  Loss of mitochondria membrane potential was detected in HK-2 cells treated with 20% postasphyxial serum as compared to cells in normal serum or PTDC-pretreated cells in 20% postasphyxial serum. A significant increase of Bad and Bax protein expression was also detected, along with the release of cytochrome C and AIF from mitochondria to cytosol in the postasphyxial serum treated cells, but not in the normal or PTDC-pretreated control cells.
  
  
  CONCLUSIONS
  Our findings suggest that postasphyxial serum may induce renal tubular cell apoptosis through the mitochondrial pathway, and its intracellular signal transduction mechanism includes the activation of nuclear factor-kappaB.
authors.affiliation: Department of Newborn Medicine, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhao
authors.forename: Wen-Bin
authors.initials: WB
authors.lastname: Dong
authors.forename: Peng-yun
authors.initials: PY
authors.lastname: Li
authors.forename: Chun-liang
authors.initials: CL
authors.lastname: Deng
mesh_terms: D017209:Apoptosis; D001238:Asphyxia Neonatorum / Q000097:blood* / Q000150:complications* / Q000628:therapy; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D003593:Cytoplasm / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D007674:Kidney Diseases / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules; D007687:Kidney Tubules, Proximal / Q000648:ultrastructure; D053078:Membrane Potential, Mitochondrial; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011759:Pyrrolidines / Q000008:administration & dosage; D015427:Reperfusion Injury / Q000209:etiology*; D044967:Serum; D015398:Signal Transduction / Q000502:physiology*; D013859:Thiocarbamates / Q000008:administration & dosage; D051028:bcl-2-Associated X Protein / Q000032:analysis; D051025:bcl-Associated Death Protein / Q000032:analysis
chemical_list: D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; C020972:pyrrolidine dithiocarbamic acid; D045304:Cytochromes c