Cytotoxicity by endocrine disruptors through effects on ER Ca 2+ transporters, aberrations in Ca 2+ signalling pathways and ER stress

Francesco Michelangeli*, Noor A. Mohammed, Brogan Jones, Monsurat Tairu, Fawaz Al‐Mousa

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Abstract

Concerns regarding man‐made organic chemicals pervading our ecosystem and having adverse and detrimental effects upon organisms, including man, have now been studied for several decades. Since the 1970s, some environmental pollutants were identified as having endocrine disrupting affects. These endocrine disrupting chemicals (EDC) were initially shown to have estrogenic or anti‐estrogenic properties and some were also shown to bind to a variety of hormone receptors. However, since the 1990s it has also been identified that many of these EDC additionally, have the ability of causing abnormal alterations in Ca2+ signalling pathways (also commonly involved in hormone signalling), leading to exaggerated elevations in cytosolic [Ca2+] levels, that is known to cause activation of a number of cell death pathways. The major emphasis of this review is to present a personal perspective of the evidence for some types of EDC, specifically alkylphenols and brominated flame retardants (BFRs), causing direct effects on Ca2+ transporters (mainly the SERCA Ca2+ ATPases), culminating in acute cytotoxicity and cell death. Evidence is also presented to indicate that this Ca2+ATPase inhibition, which leads to abnormally elevated cytosolic [Ca2+], as well as a decreased luminal ER [Ca2+], which triggers the ER stress response, are both involved in acute cytotoxicity.
Original languageEnglish
Number of pages13
JournalFEBS Open Bio
Early online date13 Aug 2024
DOIs
Publication statusE-pub ahead of print - 13 Aug 2024

Keywords

  • endocrine disrupting chemicals
  • alkylphenols
  • Ca2+ transporters
  • Ca2+ homeostasis
  • cell death
  • brominated flame retardants

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