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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

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

Katja A Puttonen, Sárka Lehtonen, Atso Raasmaja, Pekka T Männistö

Toxicol In Vitro. 2006 Dec;20(8):1446-54.

PMID: 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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP88795328	Z-Pro-prolinal		88795-32-8	Price

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