Tributyltin (TBT) salts are potent skin irritants both in humans and rodents. Data in the literature indicate mitochondria as target of TBT effects. Here, we investigate the early intracellular molecular events that follow TBT treatment and the relevance of calcium ions and mitochondria in gene-regulatory signaling pathways. Confluent HEL30 cells were treated with increasing doses of TBT (0-5 μM). At different times thereafter, the level of intracellular Ca2+, the cellular oxidative activity, nuclear factor-κB (NF-κB) activation, and IL-1α production were measured. TBT induced a dose-related increase of intracellular Ca2+ that reached the plateau 4 min following treatment. The increase of intracellular Ca2+ was followed by an increase in cellular oxidative activity as measured by DCFH oxidation (15 min) that preceded NF-κB activation (30 min) and IL-1α production (4 hr). All these events can be almost completely abrogated by BAPTA, an intracellular Ca2+ chelator. Furthermore, the modulation of cellular oxidative activity induced by TBT observed with rotenone, an inhibitor of the electron entry from complex I to ubiquinone, or after prolonged treatment with ethidium bromide, an inhibitor of mitochondrial DNA and RNA synthesis, indicates mitochondria as an important intracellular source of reactive oxygen species. These findings indicate the rise in intracellular Ca2+ as the starting event and indicate the role of mitochondria as the source of second messenger molecules essential for TBT-induced NF-κB activation and IL-1α production.

Role of mitochondria and calcium ions in tributyltin-induced gene regulatory pathways / E. Corsini, B. Viviani, M. Marinovich, C.L. Galli. - In: TOXICOLOGY AND APPLIED PHARMACOLOGY. - ISSN 0041-008X. - 145:1(1997), pp. 74-81.

Role of mitochondria and calcium ions in tributyltin-induced gene regulatory pathways

E. Corsini
Primo
;
B. Viviani
Secondo
;
M. Marinovich
Penultimo
;
C.L. Galli
Ultimo
1997

Abstract

Tributyltin (TBT) salts are potent skin irritants both in humans and rodents. Data in the literature indicate mitochondria as target of TBT effects. Here, we investigate the early intracellular molecular events that follow TBT treatment and the relevance of calcium ions and mitochondria in gene-regulatory signaling pathways. Confluent HEL30 cells were treated with increasing doses of TBT (0-5 μM). At different times thereafter, the level of intracellular Ca2+, the cellular oxidative activity, nuclear factor-κB (NF-κB) activation, and IL-1α production were measured. TBT induced a dose-related increase of intracellular Ca2+ that reached the plateau 4 min following treatment. The increase of intracellular Ca2+ was followed by an increase in cellular oxidative activity as measured by DCFH oxidation (15 min) that preceded NF-κB activation (30 min) and IL-1α production (4 hr). All these events can be almost completely abrogated by BAPTA, an intracellular Ca2+ chelator. Furthermore, the modulation of cellular oxidative activity induced by TBT observed with rotenone, an inhibitor of the electron entry from complex I to ubiquinone, or after prolonged treatment with ethidium bromide, an inhibitor of mitochondrial DNA and RNA synthesis, indicates mitochondria as an important intracellular source of reactive oxygen species. These findings indicate the rise in intracellular Ca2+ as the starting event and indicate the role of mitochondria as the source of second messenger molecules essential for TBT-induced NF-κB activation and IL-1α production.
Settore BIO/14 - Farmacologia
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/181470
Citazioni
  • ???jsp.display-item.citation.pmc??? 1
  • Scopus 30
  • ???jsp.display-item.citation.isi??? 29
social impact