Azaspiracid-1, a potent, nonapoptotic new phycotoxin with several cell targets.
This paper reports on potential cellular targets of azaspiracid-1 (AZ-1), a new phycotoxin that causes diarrhoeic and neurotoxic symptoms and whose mechanism of action is unknown. In excitable neuroblastoma cells, the systems studied were membrane potential, F-actin levels and mitochondrial membrane potential. AZ-1 does not modify mitochondrial activity but decreases F-actin concentration. These results indicate that the toxin does not have an apoptotic effect but uses actin for some of its effects. Therefore, cytoskeleton seems to be an important cellular target for AZ-1 effect. AZ-1 does not induce any modification in membrane potential, which does not support for neurotoxic effects. In human lymphocytes, cAMP, cytosolic calcium and cytosolic pH (pHi) levels were also studied. AZ-1 increases cytosolic calcium and cAMP levels and does not affect pHi (alkalinization). Cytosolic calcium increase seems to be dependent on both the release of calcium from intracellular Ca(2+) pools and the influx from extracellular media through Ni(2+)-blockable channels. AZ-1-induced Ca(2+) increase is negatively modulated by protein kinase C (PKC) activation, protein phosphatases 1 and 2A (PP1 and PP2A) inhibition and cAMP increasing agents. The effect of AZ-1 in cAMP is not extracellularly Ca(2+) dependent and insensitive to okadaic acid (OA).
Román
Yolanda
Y
Departamento de Farmacología, Facultad de Veterinaria, USC, 27002 Lugo, Spain.
Alfonso
Amparo
A
Louzao
M Carmen
MC
de la Rosa
Laura A
LA
Leira
Francisco
F
Vieites
Juan M
JM
Vieytes
Mercedes R
MR
Ofuji
Katsuya
K
Satake
Masayuki
M
Yasumoto
Takeshi
T
Botana
Luis M
LM
D008841:Actin Cytoskeleton / Q000187:drug effects; D002118:Calcium / Q000032:analysis; D002460:Cell Line; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D003600:Cytosol / Q000737:chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008387:Marine Toxins / Q000737:chemistry / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology*; D000095702:Polyether Toxins
D002118:Calcium; D000242:Cyclic AMP; D008387:Marine Toxins; D013141:Spiro Compounds; C406592:azaspiracid; D000095702:Polyether Toxins