Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues
<p>Abstract</p> <p>Background</p> <p>In prostate cancer, normal citrate-producing glandular secretory epithelial cells undergo a metabolic transformation to malignant citrate-oxidizing cells. m-Aconitase is the critical step involved in this altered citrate metabolism t...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2006-04-01
|
Series: | Molecular Cancer |
Online Access: | http://www.molecular-cancer.com/content/5/1/14 |
id |
doaj-c43c9c6deddf45da8f2fe2d7be7f16d1 |
---|---|
record_format |
Article |
spelling |
doaj-c43c9c6deddf45da8f2fe2d7be7f16d12020-11-24T21:47:08ZengBMCMolecular Cancer1476-45982006-04-01511410.1186/1476-4598-5-14Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissuesFranklin Renty BDesouki Mohamed MSingh Keshav KCostello Leslie C<p>Abstract</p> <p>Background</p> <p>In prostate cancer, normal citrate-producing glandular secretory epithelial cells undergo a metabolic transformation to malignant citrate-oxidizing cells. m-Aconitase is the critical step involved in this altered citrate metabolism that is essential to prostate malignancy. The limiting m-aconitase activity in prostate epithelial cells could be the result of a decreased level of m-aconitase enzyme and/or the inhibition of existing m-aconitase. Earlier studies identified zinc as an inhibitor of m-aconitase activity in prostate cells; and that the depletion of zinc in malignant cells is an important factor in this metabolic transformation. However, a possibility remains that an altered expression and level of m-aconitase enzyme might also be involved in this metabolic transformation. To address this issue, the in situ level of m-aconitase enzyme was determined by immunohistochemical analysis of prostate cancer tissue sections and malignant prostate cell lines.</p> <p>Results</p> <p>The immunocytochemical procedure successfully identified the presence of m-aconitase localized in the mitochondrial compartment in PC-3, LNCaP, and DU-145 malignant prostate cell lines. The examination of prostate tissue sections from prostate cancer subjects demonstrated that m-aconitase enzyme is present in the glandular epithelium of normal glands, hyperplastic glands, adenocrcinomatous glands, and prostatic intraepithelial neoplastic foci. Quantitative analysis of the relative level of m-aconitase in the glandular epithelium of citrate-producing adenomatous glands versus the citrate-oxidizing adenocarcinomatous glands revealed no significant difference in m-aconitase enzyme levels. This is in contrast to the down-regulation of ZIP1 zinc transporter in the malignant glands versus hyperplastic glands that exists in the same tissue samples.</p> <p>Conclusion</p> <p>The results demonstrate the existence of m-aconitase enzyme in the citrate-producing glandular epithelial cells; so that deficient m-aconitase enzyme is not associated with the limiting m-aconitase activity that prevents citrate oxidation in these cells. The level of m-aconitase is maintained in the malignant cells; so that an altered enzyme level is not associated with the increased m-aconitase activity. Consequently, the elevated zinc level that inhibits m-aconitase enzyme is responsible for the impaired citrate oxidation in normal and hyperplastic prostate glandular epithelial cells. Moreover, the down-regulation of ZIP1 zinc transporter and corresponding depletion of zinc results in the increase in the activity of the existing m-aconitase activity in the malignant prostate cells. The studies now define the mechanism for the metabolic transformation that characterizes the essential transition of normal citrate-producing epithelial cells to malignant citrate-oxidizing cells.</p> http://www.molecular-cancer.com/content/5/1/14 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Franklin Renty B Desouki Mohamed M Singh Keshav K Costello Leslie C |
spellingShingle |
Franklin Renty B Desouki Mohamed M Singh Keshav K Costello Leslie C Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues Molecular Cancer |
author_facet |
Franklin Renty B Desouki Mohamed M Singh Keshav K Costello Leslie C |
author_sort |
Franklin Renty B |
title |
Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues |
title_short |
Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues |
title_full |
Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues |
title_fullStr |
Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues |
title_full_unstemmed |
Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues |
title_sort |
mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues |
publisher |
BMC |
series |
Molecular Cancer |
issn |
1476-4598 |
publishDate |
2006-04-01 |
description |
<p>Abstract</p> <p>Background</p> <p>In prostate cancer, normal citrate-producing glandular secretory epithelial cells undergo a metabolic transformation to malignant citrate-oxidizing cells. m-Aconitase is the critical step involved in this altered citrate metabolism that is essential to prostate malignancy. The limiting m-aconitase activity in prostate epithelial cells could be the result of a decreased level of m-aconitase enzyme and/or the inhibition of existing m-aconitase. Earlier studies identified zinc as an inhibitor of m-aconitase activity in prostate cells; and that the depletion of zinc in malignant cells is an important factor in this metabolic transformation. However, a possibility remains that an altered expression and level of m-aconitase enzyme might also be involved in this metabolic transformation. To address this issue, the in situ level of m-aconitase enzyme was determined by immunohistochemical analysis of prostate cancer tissue sections and malignant prostate cell lines.</p> <p>Results</p> <p>The immunocytochemical procedure successfully identified the presence of m-aconitase localized in the mitochondrial compartment in PC-3, LNCaP, and DU-145 malignant prostate cell lines. The examination of prostate tissue sections from prostate cancer subjects demonstrated that m-aconitase enzyme is present in the glandular epithelium of normal glands, hyperplastic glands, adenocrcinomatous glands, and prostatic intraepithelial neoplastic foci. Quantitative analysis of the relative level of m-aconitase in the glandular epithelium of citrate-producing adenomatous glands versus the citrate-oxidizing adenocarcinomatous glands revealed no significant difference in m-aconitase enzyme levels. This is in contrast to the down-regulation of ZIP1 zinc transporter in the malignant glands versus hyperplastic glands that exists in the same tissue samples.</p> <p>Conclusion</p> <p>The results demonstrate the existence of m-aconitase enzyme in the citrate-producing glandular epithelial cells; so that deficient m-aconitase enzyme is not associated with the limiting m-aconitase activity that prevents citrate oxidation in these cells. The level of m-aconitase is maintained in the malignant cells; so that an altered enzyme level is not associated with the increased m-aconitase activity. Consequently, the elevated zinc level that inhibits m-aconitase enzyme is responsible for the impaired citrate oxidation in normal and hyperplastic prostate glandular epithelial cells. Moreover, the down-regulation of ZIP1 zinc transporter and corresponding depletion of zinc results in the increase in the activity of the existing m-aconitase activity in the malignant prostate cells. The studies now define the mechanism for the metabolic transformation that characterizes the essential transition of normal citrate-producing epithelial cells to malignant citrate-oxidizing cells.</p> |
url |
http://www.molecular-cancer.com/content/5/1/14 |
work_keys_str_mv |
AT franklinrentyb mitochondrialaconitaseandcitratemetabolisminmalignantandnonmalignanthumanprostatetissues AT desoukimohamedm mitochondrialaconitaseandcitratemetabolisminmalignantandnonmalignanthumanprostatetissues AT singhkeshavk mitochondrialaconitaseandcitratemetabolisminmalignantandnonmalignanthumanprostatetissues AT costellolesliec mitochondrialaconitaseandcitratemetabolisminmalignantandnonmalignanthumanprostatetissues |
_version_ |
1725899113976823808 |