Rao R K, Baker R D, Baker S S, Gupta A, Holycross M
Department of Pediatrics, Medical University of South Carolina, Charleston 29425, USA.
Am J Physiol. 1997 Oct;273(4):G812-23. doi: 10.1152/ajpgi.1997.273.4.G812.
The effect of hydrogen peroxide (H2O2) on intestinal epithelial barrier function was examined in Caco-2 and T84 cell monolayers. H2O2 reduced transepithelial electrical resistance (TER) of Caco-2 and T84 cell monolayers. This decrease in TER was associated with a decrease in dilution potential and an increase in [3H]mannitol permeability, suggesting an H2O2-induced disruption of the paracellular junctional complexes. H2O2 administration also induced tyrosine phosphorylation of several proteins (at the molecular mass ranges of 50-90, 100-130, and 150-180 kDa) in Caco-2 cell monolayers. Phenylarsine oxide and sodium orthovanadate, inhibitors of protein tyrosine phosphatase, decreased TER and increased mannitol permeability and protein tyrosine phosphorylation (PTP). A low concentration of sodium orthovanadate also potentiated the effect of H2O2 on TER, dilution potential, mannitol permeability, and PTP. Pretreatment with genistein (30-300 microM) and tyrphostin (100 microM) inhibited the effect of H2O2 on TER, dilution potential, mannitol permeability, and PTP. These studies show that H2O2 increases the epithelial permeability by disrupting paracellular junctional complexes, most likely by a PTP-dependent mechanism.
在Caco-2和T84细胞单层中检测了过氧化氢（H2O2）对肠道上皮屏障功能的影响。H2O2降低了Caco-2和T84细胞单层的跨上皮电阻（TER）。TER的这种降低与稀释电位的降低和[3H]甘露醇通透性的增加相关，表明H2O2诱导了细胞旁连接复合体的破坏。给予H2O2还诱导了Caco-2细胞单层中几种蛋白质（分子量范围为50-90、100-130和150-180 kDa）的酪氨酸磷酸化。蛋白质酪氨酸磷酸酶抑制剂苯砷酸氧化物和原钒酸钠降低了TER，增加了甘露醇通透性和蛋白质酪氨酸磷酸化（PTP）。低浓度的原钒酸钠也增强了H2O2对TER、稀释电位、甘露醇通透性和PTP的影响。用染料木黄酮（30-300 microM）和 tyrphostin（100 microM）预处理可抑制H2O2对TER、稀释电位、甘露醇通透性和PTP的影响。这些研究表明，H2O2通过破坏细胞旁连接复合体增加上皮通透性，最可能是通过一种依赖PTP的机制。
