| 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. |
| Authors | Katja A Puttonen, Sárka Lehtonen, Atso Raasmaja, Pekka T Männistö
(Affiliation: Department of Pharmacology and Toxicology, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. katja.puttonen at uku.fi)
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| Journal | Toxicology in vitro : an international journal published in association with BIBRA
(Toxicol In Vitro)
Vol. 20
Issue 8
Pg. 1446-54
(Dec 2006)
ISSN: 0887-2333 England |
| PMID | 16942854
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Actins
- Dipeptides
- JTP 4819
- Protease Inhibitors
- Proto-Oncogene Proteins c-bcl-2
- Pyrrolidines
- Reactive Oxygen Species
- Tetrazolium Salts
- Thiazoles
- Tumor Suppressor Protein p53
- Oxidopamine
- Cytarabine
- thiazolyl blue
- N-benzyloxycarbonylprolylprolinal
- Glyceraldehyde-3-Phosphate Dehydrogenases
- Serine Endopeptidases
- prolyl oligopeptidase
|
| Topics |
- Actins
(biosynthesis, genetics)
- Blotting, Western
- Cell Line
- Cell Survival
(drug effects)
- Cytarabine
(antagonists & inhibitors, toxicity)
- Dipeptides
(pharmacology)
- Glyceraldehyde-3-Phosphate Dehydrogenases
(metabolism)
- Humans
- Oxidopamine
(antagonists & inhibitors, toxicity)
- Protease Inhibitors
(pharmacology)
- Protein Transport
(drug effects)
- Proto-Oncogene Proteins c-bcl-2
(metabolism)
- Pyrrolidines
(pharmacology)
- Reactive Oxygen Species
(metabolism)
- Serine Endopeptidases
(metabolism)
- Tetrazolium Salts
- Thiazoles
- Tumor Suppressor Protein p53
(metabolism)
|
