Human promyelocytic leukaemia (HL-60) cells were employed to study the induction of NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme in controlling prostaglandin inactivation. Phorbol 12-myristate 13-acetate (PMA) stimulated 15-PGDH activity in a time- and concentration-dependent manner. Dimethyl sulphoxide (DMSO) also stimulated the enzyme activity, although a much delayed stimulation was observed. Western blot studies indicated that PMA increased significantly a 28 kDa immunoreactive protein characteristic of 15-PGDH. L-[35S]Methionine labelling of the PMA-treated cells showed a similar enhancement over the control cells. These studies indicate that PMA induced synthesis of 15-PGDH. Stimulation of 15-PGDH activity by PMA or DMSO appears to be mediated by protein kinase C activation, since an inactive analogue of PMA failed to induce the effect, and both staurosporine and H-7 blocked the stimulation. Stimulation by PMA was optimal at 10 nM and less effective at higher concentrations. Western blot studies indicated that a similar, if not greater, amount of enzyme protein was induced at high concentrations of PMA, suggesting that enzyme inactivation might be occurring. Possible enzyme inactivation by protein kinase C activation was further examined by incubating DMSO-treated cells with a high concentration of PMA (50 nM). Time-dependent inactivation of 15-PGDH within the first 1 h was observed and this inactivation was partially blocked by staurosporine and H-7. Pulse-chase experiments indicated that 15-PGDH had a rapid turnover rate (t 1/2 = 47 min), and PMA shortened the half-life of the enzyme (t 1/2 = 33 min), suggesting that PMA might have an additional effect on 15-PGDH degradation. The rapid turnover of 15-PGDH indicates that the enzyme activity depends on continued enzyme synthesis, and this could be susceptible to hormone and drug control mechanisms.
Rare study focuses on the health risks of children and teenagers from multiple exposure routes (MERs) of environmental media based on bioavailability of heavy metals (HMs). On the basis of considering the bioavailability of HMs, this study evaluated the multiple environmental routes and health risks to HMs in children and teenagers of eight age groups (2-<3, 3-<4, 4-<5, 5-<6, 6-<9, 9-<12, 12-<15, and 15-<18) in Beijing, China. The main findings are as follows: chromium [Cr (III)] intake by food consumption in all populations may exceed the recommended nutrient intake. And the MERs of lead in children aged 2–<3 years exceed the exposure dose (0.3 µg·kg− 1·d− 1) of 0.5 points reduction in intelligence quotient. Moreover, children aged 2–<3 and 6–<9 years have the highest non-carcinogenic risk (NCR) and carcinogenic risk (CR), respectively. The contributions of oral ingestion, dermal contact, and inhalation to the NCR were 69.5%, 18.9% and 11.6%, respectively. And the combined NCR contributions of copper, cadmium, mercury, and arsenic (As) were about 69.4%. The contributions of the above three routes to the CR were 93.4%, 4.1% and 2.5%, in that order, with the largest CR contribution of As being about 92.0%. This study can provide new ideas for accurately assessing the exposure and health risks of HMs in the population, and we believe that it is necessary to update the national standards for food and soil based on the bioavailability of HMs.
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