6 research outputs found
Isotopic evidence of unaccounted for Fe and Cu erythropoietic pathways
International audienceDespite its potential importance for understanding perturbations in the Fe-Cu homeostatic pathways, the natural isotopic variability of these metals in the human body remains unexplored. We measured the Fe, Cu, and Zn isotope compositions of total blood, serum, and red blood cells of similar to 50 young blood donors by multiple-collector ICP-MS after separation and purification by anion exchange chromatography. Zinc shows much less overall isotopic variability than Fe and Cu, which indicates that isotope fractionation depends more on redox conditions than on ligand coordination. On average, Fe in erythrocytes is isotopically light with respect to serum, whereas Cu is heavy. Iron and Cu isotope compositions clearly separate erythrocytes of men and women. Fe and Cu from B-type men erythrocytes are visibly more fractionated than all the other blood types. Isotope compositions provide an original method for evaluating metal mass balance and homeostasis. Natural isotope variability shows that the current models of Fe and Cu erythropoiesis violate mass balance requirements. It unveils unsuspected major pathways for Fe, with erythropoietic production of isotopically heavy ferritin and hemosiderin, and for Cu, with isotopically light Cu being largely channeled into blood and lymphatic circulation rather than into superoxide dismutase-laden erythrocytes. Iron isotopes provide an intrinsic measuring rod of the erythropoietic yield, while Cu isotopes seem to gauge the relative activity of erythropoiesis and lymphatics
Fe and Cu stable isotopes in archeological human bones and their relationship to sex
International audienceAccurate sex assignment of ancient human remains usually relies on the availability of coxal bones or well-preserved DNA. Iron (Fe) and copper (Cu) stable isotope compositions (56Fe/54Fe and 65Cu/63Cu, respectively) were recently measured in modern human blood, and an unexpected result was the discovery of a 56Fe-depletion and a 65Cu-enrichment in men's blood compared to women's blood. Bones, being pervasively irrigated by blood, are expected to retain the 56Fe/54Fe and 65Cu/63Cu signature of blood, which in turn is useful for determining the sex of ancient bones. Here, we report the 56Fe/54Fe, 65Cu/63Cu, and 66Zn/64Zn ratios from a suite of well-preserved phalanxes (n = 43) belonging to individuals buried in the 17th and 18th centuries at the necropolis of Saint-Laurent de Grenoble, France, and for which the sex was independently estimated from pelvic bone morphology. The metals were purified from the bone matrix by liquid chromatography on ion exchange resin and the isotope compositions were measured by multiple-collector inductively coupled plasma mass spectrometry. The results show that, as expected from literature data on blood, male bone iron is depleted in 56Fe and enriched in 65Cu relative to female. No sex difference is found in the 66Zn/64Zn ratios of bone. The concentration and isotopic data show no evidence of soil contamination. Four samples of five (77%) can be assigned their correct sex, a result comparable to sex assignment using Fe and Cu isotopes in blood (81%). Isotopic analysis of metals may therefore represent a valid method of sex assignment applicable to incomplete human remains
A search for life in Palaeoproterozoic marine sediments using Zn isotopes and geochemistry
International audienceSediments from the 2.1- to 1.9-billion-year-old Francevillian Group in southeastern Gabon include centimeter-sized pyritized structures suggestive of colonial organisms (El Albani et al., 2010), some of which may have been motile (El Albani et al., 2019). However, these interpretations were largely based on morphological and geochemical characteristics that lack metabolic clues and/or can be explained by abiotic processes. To move this work forward, we describe other centimeter-sized specimens, loosely referred to as lenticular forms (LF), from the same area and apply a more holistic approach including morphology, mineralogy, and geochemistry. The objects are 0.2–4 cm in diameter, and most of them are endowed with a regular brim that scales proportionally to external diameter reminiscent of biological order, hence rendering the LF putative biogenic traces. The LF are perfectly delineated in every direction and deflect the sedimentary layers on which they rest. X-ray microtomography further demonstrates that the LF are syn-depositional features and not concretions, while lead isotope systematics indicate that the geochemical imprint of diagenesis is inconsequential. Low sulfur content is largely concentrated in the organic matrix, and scarcity of pyrite and its persistence as micron-sized crystals show that the role of sulfate reduction is minor. Most interestingly, the fillings of the LF cavities show large and correlated excesses of organic carbon and zinc, with the latter being distinctly enriched in its light isotopes. The geochemical anomalies of the fillings relative to the host rock, notably those associated with Zn, clearly were buried with the LF, and further imply biogenicity. In this regard, a ten-fold increase in LF size towards the top of the black shale series hosting the LF might be related to increasing Zn (nutrient) availability. Although we cannot conclude with any certainty what these remnant organisms were, their features all taken together are evocative of very large agglutinate protists that grazed on bacterial biomass either in the water column or as benthic mats
Natural variations of copper and sulfur stable isotopes in blood of hepatocellular carcinoma patients
Balter, Vincent Nogueira da Costa, Andre Bondanese, Victor Paky Jaouen, Klervia Lamboux, Aline Sangrajrang, Suleeporn Vincent, Nicolas Fourel, Francois Telouk, Philippe Gigou, Michelle Lecuyer, Christophe Srivatanakul, Petcharin Brechot, Christian Albarede, Francis Hainaut, Pierre eng Research Support, Non-U.S. Gov't 2015/01/15 06:00 Proc Natl Acad Sci U S A. 2015 Jan 27;112(4):982-5. doi: 10.1073/pnas.1415151112. Epub 2015 Jan 12.International audienceThe widespread hypoxic conditions of the tumor microenvironment can impair the metabolism of bioessential elements such as copper and sulfur, notably by changing their redox state and, as a consequence, their ability to bind specific molecules. Because competing redox state is known to drive isotopic fractionation, we have used here the stable isotope compositions of copper ((65)Cu/(63)Cu) and sulfur ((34)S/(32)S) in the blood of patients with hepatocellular carcinoma (HCC) as a tool to explore the cancer-driven copper and sulfur imbalances. We report that copper is (63)Cu-enriched by approximately 0.4 per thousand and sulfur is (32)S-enriched by approximately 1.5 per thousand in the blood of patients compared with that of control subjects. As expected, HCC patients have more copper in red blood cells and serum compared with control subjects. However, the isotopic signature of this blood extra copper burden is not in favor of a dietary origin but rather suggests a reallocation in the body of copper bound to cysteine-rich proteins such as metallothioneins. The magnitude of the sulfur isotope effect is similar in red blood cells and serum of HCC patients, implying that sulfur fractionation is systemic. The (32)S-enrichment of sulfur in the blood of HCC patients is compatible with the notion that sulfur partly originates from tumor-derived sulfides. The measurement of natural variations of stable isotope compositions, using techniques developed in the field of Earth sciences, can provide new means to detect and quantify cancer metabolic changes and provide insights into underlying mechanisms