Determining baseline radiation levels in marine biota - A comparison of SE Queensland commercial species.

Limited data exists on the contribution to radiological dose to members of the public from ingestion of radioactivity in seafood in the Australian diet. There is also a lack of data available to assess the radiological dose to marine fauna in Australian waters. Natural and anthropogenic radionuclides and trace metals were measured in the edible flesh of prawns to determine the radiological dose to humans. The remaining tissues were combined and analysed to enable uptake and environmental radiological doses to be assessed. Although in international studies, the edible flesh is generally measured to determine radiation dose or ingestion of trace metals, the effects of preparation and cooking techniques are rarely assessed. In this study, cooking and preparation techniques that may influence the radiological dose to humans were assessed. Eggs were also removed from a selected number of samples to assess the potential dose in sensitive developmental tissues and possible implications for environmental effects. Order of magnitude differences in 210Po activity concentrations and Cd concentrations were observed between whole animals and the edible flesh of Australian caught King (Melicertus spp.) and Tiger (Penaeus spp.) prawns, with the hepatopancreas primarily responsible for this difference. Most 210Po was unsupported by 210Pb and activity concentrations of all other radionuclides measured (137Cs, 210Pb, 226Ra, 232Th, and 238U) were very low. The major contribution to radiation dose via the ingestion pathway and to the organism itself was from 210Po. Cooking techniques that may lead to leaching of 210Po from the hepatopancreas could substantially increase the radiological dose from ingestion of this isotope. Organism dose estimates using different input assumptions in the radiological assessment tool "ERICA", including site-specific tissue activity concentrations with site- or region-specific media concentrations, were compared with ERICA default distribution coefficients (Kd) and concentration ratios.

Cell surface rescue of kidney anion exchanger 1 mutants by disruption of chaperone interactions.

Mutations in the human kidney anion exchanger 1 (kAE1) membrane glycoprotein cause impaired urine acidification resulting in distal renal tubular acidosis (dRTA). Dominant and recessive dRTA kAE1 mutants exhibit distinct trafficking defects with retention in the endoplasmic reticulum (ER), Golgi, or mislocalization to the apical membrane in polarized epithelial cells. We examined the interaction of kAE1 with the quality control system responsible for the folding of membrane glycoproteins and the retention and degradation of misfolded mutants. Using small molecule inhibitors to disrupt chaperone interactions, two functional, dominant kAE1 mutants (R589H and R901stop), retained in the ER and targeted to the proteasome for degradation by ubiquitination, were rescued to the basolateral membrane of Madin-Darby canine kidney cells. In contrast, the Golgi-localized, recessive G701D and the severely misfolded, ER-retained dominant Southeast Asian ovalocytosis (SAO) mutants were not rescued. These results show that functional dRTA mutants are retained in the ER due to their interaction with molecular chaperones, particularly calnexin, and that disruption of these interactions can promote their escape from the ER and cell surface rescue.

Loss of specific chaperones involved in membrane glycoprotein biosynthesis during the maturation of human erythroid progenitor cells.

The production of erythrocytes requires the massive synthesis of red cell-specific proteins including hemoglobin, cytoskeletal proteins, as well as membrane glycoproteins glycophorin A (GPA) and anion exchanger 1 (AE1). We found that during the terminal differentiation of human CD34(+) erythroid progenitor cells in culture, key components of the endoplasmic reticulum (ER) protein translocation (Sec61alpha), glycosylation (OST48), and protein folding machinery, chaperones BiP, calreticulin (CRT), and Hsp90 were maintained to allow efficient red cell glycoprotein biosynthesis. Unexpected was the loss of calnexin (CNX), an ER glycoprotein chaperone, and ERp57, a protein-disulfide isomerase, as well as a major decrease of the cytosolic chaperones, Hsc70 and Hsp70, components normally involved in membrane glycoprotein folding and quality control. AE1 can traffic to the cell surface in mouse embryonic fibroblasts completely deficient in CNX or CRT, whereas disruption of the CNX/CRT-glycoprotein interactions in human K562 cells using castanospermine did not affect the cell-surface levels of endogenous GPA or expressed AE1. These results demonstrate that CNX and ERp57 are not required for major glycoprotein biosynthesis during red cell development, in contrast to their role in glycoprotein folding and quality control in other cells.