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.
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Acknowledgments
We thank Sandy Muscelli for manuscript preparation. This work was supported in part by NCI-RO1 (1 RO1 CA106644-01 to C.-A.A. Hu) and by the Intramural program of the NCI, NIH (to J.M. Phang). David Valle is an Investigator in the Howard Hughes Medical Institute.
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Hu, Ca.A., Donald, S.P., Yu, J. et al. Overexpression of proline oxidase induces proline-dependent and mitochondria-mediated apoptosis. Mol Cell Biochem 295, 85–92 (2007). https://doi.org/10.1007/s11010-006-9276-6
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DOI: https://doi.org/10.1007/s11010-006-9276-6