Hydrogen peroxide inhibits gap junctional intercellular communication in glutathione sufficient but not glutathione deficient cells

Cell to cell communication via gap junctions is essential in the maintenance of the homeostatic balance of multicellular organisms. Aberrant intercellular gap junctional communication (GJIC) has been implicated in tumor promotion, neuropathy and teratogenesis. Oxidative stress has also been implicated in similar pathologies such as cancer. We report a potential link between oxidative stress and GJIC. Hydrogen peroxide, a known tumor promoter, inhibited GJIC in WB-F344 rat liver epithelial cells with an I50 value of 200 microM. Inhibition of GJIC by H2O2 was reversible as indicated by the complete recovery of GJIC with the removal of H2O2 via a change of fresh media. Free radical scavengers, such as t-butyl alcohol, propylgallate, and Trolox, did not prevent the inhibition of GJIC by H2O2, which indicated that the effects of H2O2 on GJIC was probably not a consequence of aqueous free radical damage. The depletion of intracellular GSH reversed the inhibitory effect of H2O2 on GJIC. The treatment of glutathione- sufficient cells with H2O2 resulted in the hyperphosphorylation of connexin43, which is the basic subunit of the hexameric gap junction protein, as determined by Western blot analysis. TPA, a well-known tumor promoter, also inhibits GJIC via hyperphosphorylation of GJIC, which is a result of protein kinase-C activation. However, H2O2 also induced hyperphosphorylation in GSH-deficient cells that had normal rates of GJIC. Therefore, the mechanism of GJIC inhibition must be different from the TPA-pathway and involves GSH.      

原发性病原真菌和条件性真菌所致的甲真菌病

近40年间在易感或免疫受损个体中原发性和条件性真菌感染显著增多。其发病率的增加与艾滋病的流行和医疗技术的重大发展,尤其是器官移植、肿瘤及免疫性疾病新的治疗方法相关。在真菌性疾病中,尽管某些人群更易患甲真菌病,但每一个体均可能患该病。虽然甲真菌病呈慢性经过且并不威胁生命,但可严重影响患者的身心健康。甲真菌病的患病率在许多国家似乎呈上升趋势,范围在3%～15%。尽管临床表现可提示有真菌感染,但保证诊断正确和治疗合理仍依赖实验室检查。尽管酵母和霉菌也可成为单独或混合感染的病原菌,但大多数甲真菌病是由皮肤癣菌引起的。…