title: Fibroblasts from long-lived rodent species exclude cadmium.
abstract: Resistance to the lethal effects of cellular stressors, including the toxic heavy metal cadmium (Cd), is characteristic of fibroblast cell lines derived from long-lived bird and rodent species, as well as cell lines from several varieties of long-lived mutant mice. To explore the mechanism of resistance to Cd, we used inductively coupled plasma mass spectroscopy to measure the rate of Cd uptake into primary fibroblasts of 15 rodent species. These data indicate that fibroblasts from long-lived rodent species have slower rates of Cd uptake from the extracellular medium than those from short-lived species. In addition, fibroblasts from short-lived species export more zinc after exposure to extracellular Cd than cells from long-lived species. Lastly, fibroblasts from long-lived rodent species have lower baseline concentrations of two redox-active metals, iron and copper. Our results suggest that evolution of longevity among rodents required adjustment of cellular properties to alter metal homeostasis and to reduce the toxic effects of heavy metals that accumulate over the course of a longer life span.
authors: Department of Chemistry, University of Michigan, Ann Arbor. Department of Pathology, University of Michigan, Ann Arbor.
authors: Lubomír
authors: L
authors: Dostál
authors: Department of Pathology, University of Michigan, Ann Arbor.
authors: William M
authors: WM
authors: Kohler
authors: Department of Chemistry, University of Michigan, Ann Arbor. Department of Biophysics, University of Michigan, Ann Arbor.
authors: James E
authors: JE
authors: Penner-Hahn
authors: Department of Pathology, University of Michigan, Ann Arbor. Geriatrics Center, University of Michigan, Ann Arbor.
authors: Richard A
authors: RA
authors: Miller
authors: Department of Chemistry, University of Michigan, Ann Arbor. Department of Biological Chemistry, University of Michigan, Ann Arbor. fierke@umich.edu.
authors: Carol A
authors: CA
authors: Fierke
mesh_terms: D000818:Animals; D001693:Biological Transport, Active; D002104:Cadmium / Q000493:pharmacokinetics* / Q000633:toxicity; D002460:Cell Line; D003300:Copper / Q000378:metabolism; D006224:Cricetinae; D004351:Drug Resistance; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D000075322:Heavy Metal Poisoning; D007501:Iron / Q000378:metabolism; D008136:Longevity / Q000502:physiology*; D013058:Mass Spectrometry; D019216:Metals, Heavy / Q000378:metabolism; D051379:Mice; D011041:Poisoning / Q000378:metabolism; D012377:Rodentia / Q000378:metabolism*; D013045:Species Specificity
chemical_list: D019216:Metals, Heavy; D002104:Cadmium; D003300:Copper; D007501:Iron
keywords: Cadmium; Iron.; Longevity; Rodents; Zinc