Mechanisms involved in the swelling of erythrocytes caused by Pacific and Caribbean ciguatoxins
Contribuinte(s) |
M.A Lichtman |
---|---|
Data(s) |
01/01/2006
|
Resumo |
The mechanisms underlying the swelling of frog red blood cells (RBC), induced by Pacific (P-CTX-1) and Caribbean (C-CTX-1) ciguatoxins (CTXs), were investigated by measuring the length, width and surface of their elliptic shape. P-CTX-1 (0.5 to 5 nM) and C-CTX-1 (1 mu M) induced RBC swelling within 60 min. The CTXs-induced RBC swelling was blocked by apamin (1 mu M) and by Sr2+ (1 mu M). P-CTX-1-induced RBC swelling was prevented and inhibited by H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one(27 mu M), an inhibitor Of Soluble guanylate cyclase (sGC), and NOS blockade by NG methyl-L-arginine (L-NMA; 10 mu M). Cytochalasin D (cytD, 10 mu M) increased RBC surface and mimicked CTX effect but did not prevent the P-CTX-1-induced L-NMA-sensitive extra increase. Calculations revealed that P-CTX-1 and cytD increase RBC total surface envelop and volume. These data strongly suggest that the molecular mechanisms underlying CTXs-induced RBC swelling involve the NO pathway by an activation of the inducible NOS, leading to sGC activation which modulates intracellular cGMP and regulates L-type Ca2+ channels. The resulting increase in intracellular Ca2+ content, in turn, disrupts the actin cytoskeleton, which causes a water influx and triggers a Ca2+-activated K+ current through SK2 isoform channels. (c) 2005 Elsevier Inc. All rights reserved. |
Identificador | |
Idioma(s) |
eng |
Publicador |
Academic Press Inc Elsevier Science |
Palavras-Chave | #ciguatoxins #red blood cells #cell swelling #L-type Ca2+ channels #nitric oxide #nitric oxide synthase #soluble guanylate cyclase #cytochalasin D #Frog Myelinated Axons #Nitric-oxide #Sodium-channels #Actin Cytoskeleton #Cells #Inhibitor #Filaments #Volume #C1 #320504 Toxicology (incl. Clinical Toxicology) #780103 Chemical sciences |
Tipo |
Journal Article |