Relationship between Ornithine Decarboxylase and Cytoskeletal Organization in Cultured Human Keratinocytes: Cellular Responses to Phorbol Esters, Cytochalasins, and α-Difluoromethylornithine

Pomidor, Mary M.; Ruhl, Kimberly K.; Zheng, Ping; Song, Yingjie; Jänne, Olli A.; Tuan, Rocky S.; Hickok, Noreen J.

doi:10.1006/excr.1995.1393

Cited by 23 publications

(33 citation statements)

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“…We observed a strong expression of ODC at the periphery of the chromosomes during the second half of mitosis and during cytokinesis, a cell phase in which microtubules play essential roles. These results are in close agreement with those of previous studies (Pomidor et al 1995;Heiskala et al 1999) that indicated that changes of ODC activity and translocations are associated with rearrangements of the cytoskeleton, suggesting attachment of ODC to structural elements and/or a role of ODC in cytokinesis.…”

Section: Localization Of Odc and Az1 During Mitosissupporting

confidence: 94%

Intracellular Localization of Ornithine Decarboxylase and Its Regulatory Protein, Antizyme-1

Schipper

Cuijpers

Groot

et al. 2004

J Histochem Cytochem.

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The enzyme ornithine decarboxylase (ODC) and its regulatory protein antizyme-1 (AZ1) are key regulators in the homeostasis of polyamines. To gain more insight into the exact intracellular distribution of ODC and AZ1, we performed immunocytochemical and Green Fluorescent Protein-fluorocytochemical studies in cultured human cervix carcinoma and human prostatic carcinoma (PC-346C) cells. ODC localization patterns varied from predominantly cytoplasmic to both cytoplasmic and nuclear staining, whereas AZ1 was mostly found in the nucleus. In cells that were synchronized in the mitotic phase, localization of both ODC and AZ1 changed from perinuclear at the beginning of mitosis into nucleoplasmic at close proximity to the chromosomes during meta-, ana- and telophase. Upon completion of mitosis, localization of ODC and AZ1 was reverted back to the cytoplasm, i.e., predominantly perinuclear immediately after cytokinesis. When PC-346C cells were treated with polyamines to induce AZ1-regulated ODC degradation, ODC was predominantly found in the nucleus and colocalized with immunoreactive AZ1. A comparable accumulation of ODC and AZ1 in the nucleus was found in PC-346C cells treated with the polyamine analog SL-11093. The present study suggests that AZ1 is involved in nucleocytoplasmic shuttling of ODC, which may be a prerequisite for ODC regulation and/or function.

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Section: Localization Of Odc and Az1 During Mitosissupporting

confidence: 94%

Intracellular Localization of Ornithine Decarboxylase and Its Regulatory Protein, Antizyme-1

Schipper

Cuijpers

Groot

et al. 2004

J Histochem Cytochem.

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“…The microscopic cell images indicate that inhibition of ODC arrested cell proliferation, which is followed by cell death. The change in morphology of cells might reflect the importance of ODC activity for maintaining the cell shape (28,29).…”

Section: Resultsmentioning

confidence: 99%

New transition state–based inhibitor for human ornithine decarboxylase inhibits growth of tumor cells

Grossenbacher

Gehring

2007

Molecular Cancer Therapeutics

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Pyridoxal 5 ¶-phosphate (PLP) -dependent ornithine decarboxylase (ODC) is the key enzyme in polyamine synthesis. ODC is overexpressed in many tumor cells and thus a potential drug target. Here we show the design and synthesis of a coenzyme-substrate analogue as a novel precursor inhibitor of ODC. Structural analysis of the crystal structure of human ODC disclosed an additional hydrophobic pocket surrounding the E-amino group of its substrate ornithine. Molecular modeling methods showed favorable interactions of the BOC-protected pyridoxylornithine conjugate, termed POB, in the active site of human ODC. The synthesized and purified POB completely inhibited the activity of newly induced ODC activity at 100 Mmol/L in glioma LN229 and COS7 cells. In correlation with the inhibition of ODC activity, a timedependent inhibition of cell growth was observed in myeloma, glioma LN18 and LN229, Jurkat, COS7, and SW2 small-cell lung cancer cells if DNA synthesis and cell number were measured, but not in the nontumorigenic human aortic smooth muscle cells. POB strongly inhibited cell proliferation not only of low-grade glioma LN229 cells in a dose-dependent manner (IC 50 f50 Mmol/L) but also of high-grade glioblastoma multiforme cells. POB is much more efficient in inhibiting proliferation of several types of tumor cells than A-DL-difluoromethylornithine, the best known irreversible inhibitor of ODC. [Mol Cancer Ther 2007;6(6):1831 -9]

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“…In growing cell fractions of human keratinocytes, ODC showed a perinuclear and nuclear distribution pattern. When cell growth was arrested, ODC distribution became more diffuse and cytoplasmic (Pomidor et al 1995).…”

Section: Discussionmentioning

confidence: 99%

Immunocytochemical Detection of Ornithine Decarboxylase

Schipper

Romain

Otten

et al. 1999

J Histochem Cytochem.

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SUMMARYOrnithine decarboxylase (ODC), a regulatory enzyme of polyamine biosynthesis, is involved in cell growth and differentiation. Lack of information about the exact cellular and subcellular localization of ODC is one of the main obstacles to precise interpretation of the biological roles of the ODC/polyamine system. Here we describe the development and optimization of an immunocytochemical method to detect ODC in cells and tissues. For this purpose a monoclonal antibody (MP16-2) against a defined epitope of ODC protein was developed. Specificity of the antibody for ODC was substantiated by Western blotting and ELISA analysis using cell and tissue homogenates. In cultured cells, optimal staining results were obtained after fixation with crosslinking fixatives followed by permeabilization with methanol. In rat tissues, ODC immunoreactivity was best preserved in paraffin sections fixed with Bouin's fixative. Antigen retrieval using SDS and citrate buffer substantially increased ODC immunostaining and decreased background staining. Localization studies of ODC in different cell lines showed that strongest staining for ODC was found in the nucleoplasm of mitotic cells, whereas confluent cells showed moderate perinuclear staining. Immunocytochemical studies of various rat tissues showed high cytoplasmic immunostaining of ODC in epithelial cells of kidney, prostate, and adrenal medulla of testosterone-treated rats, in glandular epithelium of small intestine, and in pancreas of neonatal and adult rats.

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Relationship between Ornithine Decarboxylase and Cytoskeletal Organization in Cultured Human Keratinocytes: Cellular Responses to Phorbol Esters, Cytochalasins, and α-Difluoromethylornithine

Cited by 23 publications

References 0 publications

Intracellular Localization of Ornithine Decarboxylase and Its Regulatory Protein, Antizyme-1

Intracellular Localization of Ornithine Decarboxylase and Its Regulatory Protein, Antizyme-1

New transition state–based inhibitor for human ornithine decarboxylase inhibits growth of tumor cells

Immunocytochemical Detection of Ornithine Decarboxylase

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