ucf-101 and Asphyxia-Neonatorum

To investigate the expression of serine protease Omi/HtrA2 in kidneys of postasphyxial neonatal rats, and to study the effects of Ucf-101 on apoptosis and the expression of Omi/HtrA2 in these rats.. Seventy-two neonatal Wistar rats of 7-10 days old were randomly divided into 3 groups: control, postasphyxial model, Ucf-101-treated postasphyxialThe postasphyxial model was established by normobaric asphyxiaExpression of Omi/HtrA2 was determined with streptavidin-peroxidase immunohistochemistry 2, 24 and 48 hrs after asphyxia. Terminal deoxynuleotidyl-mediated nick end labeling (TUNEL) was used to ascertain the apoptosis of renal cells.. Compared with the control group, OmiHtrA2 expression in renal cells began to increase 2 hrs after asphyxia and peaked at 24 hrs. The expression of Omi/HtrA2 in the Ucf-101-treated postasphyxial group was significantly lower than that in the postasphyxial model group (P<0.01). TUNEL-positive cells began to increase 2 hrs after asphyxia and peaked at 24 hrs in the postasphyxial model group when compared with the control group. The number of TUNEL-positive cells in the Ucf-101-treated postasphyxial group was significantly lower than that in the postasphyxial model group at all time points (P<0.01).. The expression of Omi/HtrA2 in kidneys is increased in postasphyxial neonatal rats. The increased Omi/HtrA2 expression may play an important role in the development of postasphyxial renal injury. Treatment with Ucf-101 can reduce the expression of Omi/HtrA2 in kidneys of postasphyxial neonatal rats and thus reduce renal tububar epithelial cell apoptosis.

Topics: Animals; Animals, Newborn; Apoptosis; Asphyxia Neonatorum; Female; High-Temperature Requirement A Serine Peptidase 2; Humans; Immunohistochemistry; In Situ Nick-End Labeling; Infant, Newborn; Kidney; Male; Mitochondrial Proteins; Pyrimidinones; Rats; Rats, Wistar; Serine Endopeptidases; Thiones

To investigate the mechanism of inducing apoptosis of Omi/HtrA2 in renal tubular cells with post asphyxial serum of neonate.. Human renal proximal tubular cell line HK-2 cell was used as target cell. They were divided into three groups: control group, asphyxia group and Ucf-101 (Omi/HtrA2 special inhibitor) treated group. The challenge concentration of serum obtained from neonates 24 hours after asphyxia was 20%, and the treatment concentration of Ucf-101 was 10 mumol/L. The Omi/HtrA2 translocation in renal tubular cells was observed with confocal microscopy, and the rate of apoptosis was detected with flow cytometer.. It was found that Omi/HtrA2 was translocated into cytoplasm in asphyxia group, and the rate of Omi/HtrA2 translocation in HK-2 cells of asphyxia group was significantly increased [(28.1+/-3.6)% vs. (9.4+/-2.1)%, P<0.01]. Compared with the control group, after being treated with post asphyxial serum, the rate of apoptosis of HK-2 cells in asphyxia group was significantly increased [(36.3+/-4.4)% vs.(12.4+/-2.9)%, P<0.01]. Compared with asphyxia group, the rate of apoptosis in HK-2 cells in Ucf-101 treated group was significantly decreased [(27.0+/-3.9)% vs.(36.3+/-4.4)%, P<0.01].. These experimental data demonstrates that post asphyxial serum of neonate can induce apoptosis of HK-2 cells, and translocation of Omi/HtrA2 from mitochondria into cytoplasm may play an important role in its intracellular signal transduction mechanism in induction of apoptosis.

Topics: Apoptosis; Asphyxia Neonatorum; Cell Line; Cytoplasm; Epithelial Cells; High-Temperature Requirement A Serine Peptidase 2; Humans; Infant, Newborn; Kidney Tubules, Proximal; Mitochondria; Mitochondrial Proteins; Protein Transport; Pyrimidinones; Serine Endopeptidases; Serum; Signal Transduction; Thiones