Han KH. Electrolyte Blood Press. 2011 Dec;9(2):45-49. http://dx.doi.org/10.5049/EBP.2011.9.2.45

Renal ischemic events open tight junctions and disrupt epithelial polarity. The purpose of this study was to examine the effects of ischemia–reperfusion (IR) injury on expression and distribution of the tight junction proteins, occludin and ZO-1, in the rat kidney. IR injury was induced by clamping both renal pedicles for 30 min and animals were killed at 6 h after the reperfusion. IR injury decreased blood bicarbonate level, but did not persistently alter pH, Na⁺, K⁺, or Cl⁻. In control kidneys, occludin immunoreactivity was intense in the tight junctions in the thick ascending limb, distal convoluted tubule, and collecting duct, moderate in the thin limbs of the loop of Henle, and was not detected in the proximal tubule, glomerulus, and blood vessels. ZO-1 was expressed in the same sites in which occludin was expressed, and additionally was also expressed in the proximal tubule, glomerulus, and vascular endothelial cells. IR kidneys exhibited damaged renal tubular epithelial cells in both proximal tubule and collecting duct segments in the outer medulla. In the collecting duct, the response of intercalated cells and principal cells differed. Following IR injury, intercalated cells, but not principal cells, lost their normal epithelial polarity and were frequently extruded into the tubule lumen. Occludin, instead of being localized to tight junctions, was localized diffusely in the cytoplasm in intercalated cells of IR kidneys. Principal cells, in contrast, were not detectably affected and neither occludin nor ZO-1 expression were altered in response to IR injury. The normal localization of ZO-1 expression to tight junction sites in both the proximal tubule and collecting duct was altered in response to IR, and, instead, ZO-1 expression was present diffusely in the cytoplasm. IR injury did not alter detectably either occludin or ZO-1 localization to the tight junction of the thick ascending limb cells. The abundance of total occludin protein by immunoblot analysis was not changed with IR injury. These results demonstrate that renal IR injury causes tight junction disruptions in both the proximal tubule and the collecting duct, and that altered distribution of the tight junction protein, occludin, may play a critical role in the collecting duct dysfunction which IR induces.

Aims: Altered redox state has been related to the development of normal pregnancy (NP) and preeclampsia (PE). Endothelial K _Ca 2.3 and K _Ca 3.1 (K _Ca s) play an important role in vasodilation, and K _Ca s levels are affected by oxidative stress. We investigated the mechanisms of oxidative stress-mediated K _Ca s expression modulation during NP and PE. Results: Human uterine microvascular endothelial cells were incubated in serum from normal nonpregnant women ( n = 13) and women with NP ( n = 24) or PE ( n = 15), or in vascular endothelial growth factor (VEGF), oxidized low-density lipoprotein (ox-LDL), progesterone, or estradiol-17β (E ₂ )-containing medium for 24 h. NP serum elevated H ₂ O ₂ levels via reducing catalase and glutathione peroxidase 1 levels, thereby enhancing K _Ca s levels via a H ₂ O ₂ /fyn/extracellular signal-regulated kinase (ERK)-mediated pathway. VEGF enhanced H ₂ O ₂ and K _Ca s levels and K _Ca 3.1 currents. K _Ca s were upregulated and K _Ca s activation-induced endothelium-dependent relaxation (EDR) was augmented in vessels from pregnant mice and rats. Whereas PE serum, ox-LDL, progesterone, or soluble fms-like tyrosine kinase 1 (sFlt-1) elevated superoxide levels via elevating NADPH oxidase 2 (NOX2) and NOX4 levels and reducing superoxide dismutase (SOD) 1 levels, thereby downregulating K _Ca s. sFlt-1 inhibited EDR. PE serum- or progesterone-induced alterations in levels of K _Ca s were reversed by polyethylene glycol-SOD, NOX inhibition, or E ₂ . Innovation and Conclusions: This is the first study of how endothelial K _Ca s levels are modulated during NP and PE. K _Ca s were upregulated by soluble serum factors such as VEGF via H ₂ O ₂ generation in NP, and were downregulated by serum factors such as progesterone and ox-LDL via superoxide generation in PE, which may contribute to hemodynamic adaptations in NP or to the development of PE.

Fetal programming implies that the maternal diet during pregnancy affects the long-term health of offspring. Although maternal diet influences metabolic disorders and non-alcoholic fatty liver disease in offspring, the hepatic mechanisms related to metabolites are still unknown. Here, we investigated the maternal diet-related alterations in metabolites and the biological pathway in male offspring at three months of age. Pregnant rats were exposed to 50% food restriction during the prenatal period or a 45% high-fat diet during the prenatal and postnatal periods. The male offspring exposed to food restriction and high-fat diets had lower birth weights than controls, but had a catch-up growth spurt at three months of age. Hepatic taurine levels decreased in both groups compared to controls. The decreased hepatic taurine levels in offspring affected excessive lipid accumulation through changes in hepatocyte nuclear factor 4 A methylation. Moreover, the alteration of gluconeogenesis in offspring exposed to food restriction was observed to a similar extent as that of offspring exposed to a high fat diet. These results indicate that maternal diet affects the dysregulation in hepatic metabolism through changes in taurine levels and HNF4A methylation, and predisposes the offspring to Type 2 diabetes and non-alcoholic fatty liver disease in later life.

Lee SY, et al. J Vet Sci. 2013 Dec;14(4):381-386. https://doi.org/10.4142/jvs.2013.14.4.381