Comparison of intracellular zinc signals in nonadherent lymphocytes from young-adult and elderly donors: role of zinc transporters (Zip family) and proinflammatory cytokines
| Autor: | Eugenio Mocchegiani, Franco Busco, Marco Malavolta, Laura Costarelli, Nazzarena Gasparini, Gianni Bernardini, Roberta Galeazzi, Robertina Giacconi |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male medicine.medical_specialty Aging Endocrinology Diabetes and Metabolism Clinical Biochemistry chemistry.chemical_element Zinc Biology Biochemistry Peripheral blood mononuclear cell Proinflammatory cytokine Cell Line Immune system Internal medicine medicine Cell Adhesion Humans Polycyclic Compounds Lymphocytes Molecular Biology Cation Transport Proteins Aged Aged 80 and over Inflammation Nutrition and Dietetics Interleukin-6 Tumor Necrosis Factor-alpha medicine.disease Up-Regulation Endocrinology chemistry Chronic Disease Zinc deficiency Leukocytes Mononuclear Tumor necrosis factor alpha Female Efflux Intracellular Signal Transduction |
| Zdroj: | The Journal of nutritional biochemistry. 23(10) |
| ISSN: | 1873-4847 |
| Popis: | Intracellular zinc homeostasis is crucial in regulating the inflammatory/immune response at any age. It is tightly regulated by zinc transporters that control influx, efflux and compartmentalization of zinc within the cells. Specific methods for detecting the age-related differences in intracellular zinc signaling are poorly described. We report a novel assay induced after the in vitro zinc addition in peripheral blood mononuclear cells (PBMCs) and in lymphocytes from young and old donors in the absence/presence of in vitro zinc depletion (using EDTA). The intracellular labile zinc variations are monitored over time by flow cytometry using Fluozin-3 AM probe. The best curve fit of the data is calculated using a nonlinear regression model defined as follows: pr3/[1+Exp(−pr1−pr2⁎Xt)]. Pr1 depends on the initial free zinc value (time 0); pr2 describes the rate of the speed in reaching the maximum intracellular free zinc concentration; pr3 represents the maximum intracellular zinc increment (plateau curve); Xt is the time course. Age-related intracellular free zinc variations occur in PBMCs and lymphocytes incubated in EDTA-supplemented medium. The higher plateau of the curve (pr3) was observed in younger subjects. An up-regulation of Zip genes (Zip1, Zip2, Zip3), influencing zinc influx, is more pronounced in the young than old donors. Interleukin-6 and tumor necrosis factor-α overproduction was enhanced in old individuals, suggesting the presence of more marked zinc deficiency and chronic inflammation. In conclusion, the determination of intracellular zinc signals induced by in vitro zinc addition using logistic parameters may be useful to estimate the rate of intracellular zinc homeostasis and its role in inflammatory/immune response in aging. |
| Databáze: | OpenAIRE |
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