calpain and Fetal-Hypoxia

We investigated the role of beta(1) integrin in acute renal tubular injury caused by intrauterine asphyxia of neonatal rabbits by exploring the distribution and expression changes in beta(1) integrin and its mRNA in renal tubular epithelial cells.. A catheter was used to temporarily block the abdominal aortas of New Zealand pregnant rabbits in order to set up the intrauterine asphyxia animal model. The rabbit pups were randomly divided into control, asphyxia, and calpain inhibitor intervention groups and their renal tubular tissues were examined at 2 h after asphyxia. Immunofluorescence and in situ hybridization were used to examine the expression of beta(1) integrin and its mRNA, respectively. Western blot analysis was used to show the proteolysis of beta(1) integrin. Calpain inhibitor I was used to show the protective effect of keeping beta(1) integrin from being hydrolyzed after asphyxia.. (1) Normally, beta(1) integrin was located exclusively at the basal surface of renal tubular epithelial cells. After asphyxia a large amount of beta(1) integrin shifted from the basal surface to the cytoplasma and the lateral and apical surfaces and its expression decreased significantly, with simultaneous damage to renal tubular integrity and structure, many exfoliated cells and cell fragments obstructed the tubular lumen. (2) The mRNA of beta(1) integrin was mainly expressed in the cytoplasma. After asphyxia its expression increased significantly. (3) Proteolysis of beta(1) integrin was evident after asphyxia, but was significantly reduced in the calpain inhibitor intervention group. Calpain inhibitor I prevented the decrease and dislocation of beta(1) integrin and protected renal tubular integrity and structure.. Intrauterine asphyxia caused proteolysis of beta(1) integrin, with reduced expression and depolarized distribution, leading to tubular lumen obstruction and renal tubule destruction. Damage to beta(1) integrin and the renal tubule was related to the activation of calpain, and calpain inhibitor curtailed these effects.

Topics: Animals; Animals, Newborn; Calpain; Epithelial Cells; Female; Fetal Hypoxia; Integrin beta1; Kidney Diseases; Kidney Tubules; Pregnancy; Rabbits; RNA, Messenger

Perinatal hypoxia/ischemia (H/I) is the leading cause of neurological injury resulting from birth complications and pre-maturity. Our studies have demonstrated that this injury depletes the subventricular zone (SVZ) of progenitors. In this study, we sought to reveal which cell death pathways are activated within these progenitors after H/I. We found that calpain activity is detected as early as 4 h of reperfusion and is sustained for 48 h, while caspase 3 activation does not occur until 8 h and peaks at 24 h post-insult. Activated calpains and caspase 3 co-localized within precursors situated in the lateral aspects of the SVZ (which coincides with progenitor cell death), whereas neither enzyme was activated in the medial SVZ (which harbors the neural stem cells that are resilient to this insult). These studies reveal targets for neuroprotective agents to protect precursors from cell death towards the goal of restoring normal brain development after H/I.

Topics: Animals; Animals, Newborn; Apoptosis Regulatory Proteins; Calpain; Caspase 3; Cell Death; Enzyme Activation; Female; Fetal Hypoxia; Hypoxia-Ischemia, Brain; Lateral Ventricles; Male; Neurons; Rats; Rats, Wistar; Signal Transduction; Stem Cells; Telencephalon