Overexpression of proline oxidase induces proline-dependent and mitochondria-mediated apoptosis.

Article Details

Citation

Copy to clipboard

Hu CA, Donald SP, Yu J, Lin WW, Liu Z, Steel G, Obie C, Valle D, Phang JM

Overexpression of proline oxidase induces proline-dependent and mitochondria-mediated apoptosis.

Mol Cell Biochem. 2007 Jan;295(1-2):85-92. Epub 2006 Jul 28.

PubMed ID

16874462 [ View in PubMed

]

Abstract

Proline oxidase (POX), a mitochondrial inner-membrane protein, catalyzes the rate-limiting oxidation of proline to pyrroline- 5-carboxylate (P5C). Previously we showed that overexpression of POX is associated with generation of reactive oxygen species (ROS) and apoptosis in POX-inducible colorectal cancer cells, DLD-1.POX. We also showed expression of mitochondrial MnSOD partially blunts POX-induced ROS generation and apoptosis. To further investigate the molecular basis of POX-induced apoptosis, we utilized the DLD-1.POX cells to show that cells overproducing POX exhibit an L-proline-dependent apoptotic response. The apoptotic effect is specific for L-proline, detectable at 0.2 mM, maximal at 1 mM, and occurs during 48-72 h following the addition of L-proline to cells with maximally induced POX. The apoptotic response is mitochondria-mediated with release of cytochrome c, activation of caspase-9, chromatin condensation/DNA fragmentation, and cell shrinkage. We conclude that in the presence of proline, high POX activity is sufficient to induce mitochondria-mediated apoptosis.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Proline	Pyrroline-5-carboxylate reductase 1, mitochondrial	Protein	Humans	Unknown	Not Available	Details