A prolyl oligopeptidase inhibitor, Z-Pro-Prolinal, inhibits glyceraldehyde-3-phosphate dehydrogenase translocation and production of reactive oxygen species in CV1-P cells exposed to 6-hydroxydopamine.
Toxicol In Vitro
; 20(8): 1446-54, 2006 Dec.
Article
de En
| MEDLINE
| ID: mdl-16942854
ABSTRACT
We studied the ability of prolyl oligopeptidase (POP) inhibitors, Z-Pro-Prolinal and JTP-4819, to prevent translocation of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and formation of reactive oxygen species (ROS), in 6-hydroxydopamine (6-OHDA) and cytosine arabinoside (Ara-C) treated monkey fibroblast (CV1-P) and human neuroblastoma (SH-SY5Y) cells. The cells were pretreated with POP inhibitors (30 min) before addition of toxicants. GAPDH was analyzed by Western hybridization, ROS by fluorescent 2'7'-dichlorodihydro-fluorescein diacetate, and viability by the MTT method. Both toxicants induced GAPDH translocation to the particulate fraction (mitochondria and nuclei). Z-Pro-Prolinal was able to inhibit the translocation in 6-OHDA-exposed CV1-P cells. In SH-SY5Y cells and in JTP-4819 pretreated cells, no prevention of translocation was seen. However, the intensity of GAPDH in cytosolic fraction increased. Both inhibitors blocked 6-OHDA-induced ROS-production to the control level in CV1-P but, not in SH-SY5Y cells, without affecting their viability. In conclusion, POP inhibitors are able to prevent certain cell stress related factors such as ROS production or GAPDH translocation.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Inhibiteurs de protéases
/
Serine endopeptidases
/
Oxidopamine
/
Espèces réactives de l'oxygène
/
Dipeptides
/
Glyceraldehyde 3-phosphate dehydrogenases
Limites:
Humans
Langue:
En
Journal:
Toxicol In Vitro
Sujet du journal:
TOXICOLOGIA
Année:
2006
Type de document:
Article
Pays d'affiliation:
Finlande