Calcium/calmodulin signaling elicits release of cytochrome c during 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced apoptosis in the human lymphoblastic T-cell line, L-MAT

Daisuke Kobayashi, Sohel Ahmed, Masato Ishida, Shuya Kasai, Hideaki Kikuchi

Research output: Contribution to journalArticlepeer-review

24 Citations (Scopus)

Abstract

We have reported previously that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces apoptosis in the human lymphoblastic T-cell line L-MAT, although these cells do not express the aromatic hydrocarbon receptor (AhR). The AhR-dependent pathway for the induction of immunotoxicity by TCDD has been studied extensively, but the AhR-independent pathway is not understood. Several studies have reported that TCDD elevates the concentration of free intracellular calcium ([Ca2+]i) in various types of cells. However, the precise mechanism of the increase in [Ca2+]i that occurs during apoptosis induced by TCDD has not been elucidated. Upon treatment of L-MAT cells with 20 nM TCDD, we observed an early increase in [Ca2+]i, within 30 min of the addition of TCDD, which was followed by an additional increase at 90 min, after which the increase in [Ca2+]i was sustained until 3 h after the addition of TCDD. A chelator of intracellular calcium, 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetra(acetoxymethyl ester) (BAPTA-AM), blocked the induction of apoptosis by TCDD in L-MAT cells, but EGTA, a chelator of extracellular calcium, did not. An antagonist of calcium-dependent calmodulin (CaM), W-7, inhibited the induction of apoptosis by TCDD in L-MAT cells. Moreover, W-7 suppressed the mitochondrial release of cytochrome c to the cytosol. These results demonstrate that activated Ca2+/CaM could transmit apoptotic signal(s) to mitochondria. The results suggest that Ca2+/CaM signals may play an important role in the induction of apoptosis in L-MAT cells by TCDD.

Original languageEnglish
Pages (from-to)25-32
Number of pages8
JournalToxicology
Volume258
Issue number1
DOIs
Publication statusPublished - 2009 Apr 5
Externally publishedYes

Keywords

  • Apoptosis
  • Calcium
  • Calmodulin
  • Dioxin
  • Lymphoblastic T-cell line

ASJC Scopus subject areas

  • Toxicology

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