The gender differences in health effects of environmental cadmium exposure and potential mechanisms

On a viewpoint of gender differences in Cd body burden and its health effects, we reviewed the population-based research including our own which conducted in Japan, Thailand, Australia, Poland, Belgium and Sweden to assess health effects of human exposure to environmental cadmium and their potential mechanisms. As a result, six risk factors in Cd health effects in women have been identified; (1) more serious type of renal tubular dysfunction, (2) difference in calcium metabolism and its regulatory hormones, (3) kidney sensitivity; difference in P450 phenotype, (4) pregnancy, (5) body iron store status, and (6) genetic factors. Further studies of Cd toxicity targeted to women would now appear necessary.     

Prostaglandin D2 induces heme oxygenase-1 in human retinal pigment epithelial cells

The retinal pigment epithelium (RPE) constitutes the blood-retinal barrier, whose function is impaired in various pathological conditions, including cerebral malaria, a lethal complication of Plasmodium falciparum infection. Prostaglandin (PG) D₂ is abundantly produced in the brain to regulate sleep responses. Moreover, PGD₂ is a potential factor derived from intra-erythrocyte falciparum parasites. Heme oxygenase-1 (HO-1) is important for iron homeostasis via catalysis of heme degradation to release iron, carbon monoxide and biliverdin/bilirubin, and may influence iron supply to the intra-erythrocyte falciparum parasites. Here, we showed that treatment of human RPE cell lines, ARPE-19 and D407, with PGD₂ significantly increased the expression levels of HO-1 mRNA, in a dose- and time-dependent manner. Transient expression assays showed that PGD₂ treatment increased the HO-1-gene promoter activity through the enhancer sequence, containing a Maf-recognition element. Thus, PGD₂ may contribute to the maintenance of heme homeostasis in the brain by inducing HO-1 expression.