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Published on: December 27, 2016
Azaspiracids modulate intracellular pH levels in human lymphocytes
Amparo Alfonso1, Mercedes R Vieytes, Katsuya Ofuji
1Departamento de Farmacología, Facultad de Veterinaria, USC, Campus Universitario s/n, 27002 Lugo, Spain.
Biochemical and Biophysical Research Communications
|June 24, 2006
Summary
Marine toxins called azaspiracids (AZAs) affect intracellular pH and calcium levels in human lymphocytes. Specific AZAs like AZA-3 and AZA-4 show distinct effects on pH, influenced by extracellular calcium.
Area of Science:
- Marine Toxinology
- Cellular Physiology
- Biochemistry
Background:
- Azaspiracids (AZAs) are marine toxins linked to intoxications with unknown mechanisms.
- Five naturally occurring AZAs (AZA-1 to -5) and four synthetic analogues were investigated.
Purpose of the Study:
- To investigate the effects of AZAs on intracellular pH (pHi) in human lymphocytes.
- To determine the influence of extracellular calcium (Ca2+) on these pHi modulations.
Main Methods:
- Measurement of intracellular pH in human lymphocytes exposed to AZAs.
- Experiments conducted in both Ca2+-containing and Ca2+-free media.
- Inhibition studies using Ni2+ and thapsigargin (Tg) to probe Ca2+ channels.
Main Results:
- AZA-3 and AZA-4 significantly modulated intracellular pH, with effects dependent on extracellular Ca2+.
- AZA-1, AZA-2, and AZA-5 did not alter intracellular pH.
- Synthetic analogues showed varied effects on pHi and Ca2+ modulation, suggesting structure-activity relationships.
Conclusions:
- Specific azaspiracids (AZA-3, AZA-4) influence intracellular pH, demonstrating a Ca2+-dependent mechanism.
- A structure-activity relationship exists for the effects of AZAs on intracellular pH and Ca2+ coupling.
- These findings provide insights into the cellular mechanisms of azaspiracid toxicity.
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