title: Zinc induces caspase-dependent mitochondrial pathway of the programmed cell death in haemocytes of Drosophila melanogaster.
abstract: Zinc is an essential trace element in cells. However, its high level in cytoplasm promotes activation of stress signaling pathways and may lead to cell death. In the present study we used Drosophila melanogaster blood cells (haemocytes), obtained from the third instar larvae, to study the effects of high concentrations of Zn(2+) on programmed cell death (PCD). We analyzed the activity of caspases, the level of caspase inhibitor protein DIAP1 and metallothioneins, as well as calcium concentrations and activity of mitochondria in haemocytes exposed to 0.35 and 1.7 mM concentrations of Zn. The obtained results showed that rapid increase of [Zn(2+)]( i ) in the cytoplasm up-regulates metallothionein MtnB but not MtnA gene expression in cells treated with Zn(2+) in both concentrations. Excess of Zn(2+) also induced activation of the initiator caspase Dronc, associated with the mitochondrial pathway of PCD, and the effector caspase DrICE. In turn, the activity of receptor-regulated Dredd caspase was not changed. The level of DIAP1 decreased significantly in haemocytes in the presence of high Zn(2+) concentration in comparison to untreated cells. Moreover, mitochondrial membrane potential was significantly decreased after exposure to Zn ions. These results indicate that high concentration of Zn(2+) in the cytoplasm of haemocytes induces PCD via a mitochondrial pathway and that caspases play a pivotal role in this process.
authors.affiliation: Department of Cell Biology and Imaging, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387, Kraków, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Filipiak
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Tylko
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Pyza
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000378:metabolism; D004331:Drosophila melanogaster; D006434:Hemocytes / Q000187:drug effects* / Q000378:metabolism*; D007150:Immunohistochemistry; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015032:Zinc / Q000494:pharmacology*
chemical_list: D029721:Drosophila Proteins; D020169:Caspases; D015032:Zinc; D002118:Calcium