High activity of mitochondrial glycerophosphate dehydrogenase and glycerophosphate-dependent ROS production in prostate cancer cell lines
Abstract
Most malignant cells are highly glycolytic and produce high levels of reactive oxygen species (ROS) compared to normal cells. Mitochondrial glycerophosphate dehydrogenase (mGPDH) participates in the reoxidation of cytosolic NADH by delivering reducing equivalents from this molecule into the electron transport chain, thus sustaining glycolysis. Here, we investigate the role of mGPDH in maintaining an increased rate of glycolysis and evaluate glycerophosphate-dependent ROS production in prostate cancer cell lines (LNCaP, DU145, PC3, and CL1). Immunoblot, polarographic, and spectrophotometric analyses revealed that mGPDH abundance and activity was significantly elevated in prostate cancer cell lines when compared to the normal prostate epithelial cell line PNT1A. Furthermore, both the glycolytic capacity and glycerophosphate-dependent ROS production was increased 1.68- to 4.44-fold and 5- to 7-fold, respectively, in prostate cancer cell lines when compared to PNT1A cells. Overall, these data demonstrate that mGPDH is involved in maintaining a high rate of glycolysis and is an important site of electron leakage leading to ROS production in prostate cancer cells.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Increased GPDH activity has been detected in prostate cancer cells, insulinomas, and carcinoid tumors.
“In fact, increased activity of GPDH has been detected in prostate cancer cells, insulinomas and carcinoid tumors (Chowdhury et al., 2005; MacDonald et al., 1990).”
From The emerging hallmarks of cancer metabolism (2016) · cites this paper as Chowdhury et al., 2005
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
On Respiratory Impairment in Cancer Cells
Warburg, O. H. (1956) · Science · doi:10.1126/science.124.3215.269 · Cited by 3,472 · see citing works
Landis, S., Murray, T., Bolden, S., & Wingo, P. A. (1999) · CA A Cancer Journal for Clinicians · doi:10.3322/canjclin.49.1.8 · Cited by 3,068 · see citing works
THE MITOCHONDRIAL DEATH/LIFE REGULATOR IN APOPTOSIS AND NECROSIS
Kroemer, G., Dallaporta, B., & Resche-Rigon, M. (1998) · Annual Review of Physiology · doi:10.1146/annurev.physiol.60.1.619 · Cited by 1,971 · see citing works
Oxidants and human disease: some new concepts 1
Halliwell, B. B. (1987) · The FASEB Journal · doi:10.1096/fasebj.1.5.2824268 · Cited by 1,206 · see citing works
The internal structure of mitochondria
Frey, T., & Mannella, C. A. (2000) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(00)01609-1 · Cited by 902 · see citing works
The contribution of endogenous sources of DNA damage to the multiple mutations in cancer
Jackson, A. L., & Loeb, L. A. (2001) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(01)00091-4 · Cited by 630 · see citing works
Barja, G. (1999) · Journal of Bioenergetics and Biomembranes · doi:10.1023/a:1005427919188 · Cited by 494 · see citing works
Role of Mitochondria in Oxidative Stress and Aging
Lenaz, G., Bovina, C., D’Aurelio, M., Fato, R., Formiggini, G., Genova, M. L., GIULIANO, G., Pich, M. M., Paolucci, U., Castelli, G. P., et al. (2002) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2002.tb02094.x · Cited by 489 · see citing works
NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells
Brar, S. S., Corbin, Z. A., Kennedy, T. P., Hemendinger, R. A., Thornton, L., Bommarius, B., Arnold, R. S., Whorton, A. R., Sturrock, A., Huecksteadt, T. P., et al. (2003) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00525.2002 · Cited by 259 · see citing works
Cussenot, O., Berthon, P., Berger, R., Mowszowicz, I., Faille, A., Hojman, F., Teillac, P., Duc, A. L., & Calvo, F. M. (1991) · The Journal of Urology · doi:10.1016/s0022-5347(17)37953-3 · Cited by 150 · see citing works
Mitochondria metabolite transport
Klingenberg, M. (1970) · FEBS Letters · doi:10.1016/0014-5793(70)80044-8 · Cited by 146 · see citing works
Pathak, S., Sharma, R. A., Steward, W. P., Mellon, J. K., Griffiths, T. R. L., & Gescher, A. (2004) · European Journal of Cancer · doi:10.1016/j.ejca.2004.09.028 · Cited by 129 · see citing works
Renner, K., Amberger, A., Konwalinka, G., Kofler, R., & Gnaiger, E. (2003) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/s0167-4889(03)00105-8 · Cited by 123 · see citing works
Drahota, Z., Chowdhury, S. R., Floryk, D., Mráček, T., Wilhelm, J., Rauchová, H., Lenaz, G., & Houštěk, J. (2002) · Journal of Bioenergetics and Biomembranes · doi:10.1023/a:1015123908918 · Cited by 106 · see citing works
Self-citationMitochondrial Events in the Life and Death of Animal Cells: A Brief Overview
Pedersen, P. L. (1999) · Journal of Bioenergetics and Biomembranes · doi:10.1023/a:1005453700533 · Cited by 96 · see citing works
Calcium Activation of Mitochondrial Glycerol Phosphate Dehydrogenase Restudied
MacDonald, M. J., & Brown, L. J. (1996) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1996.0049 · Cited by 84 · see citing works
Brown, L. A., Koza, R. A., Everett, C. A., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202408200 · Cited by 78 · see citing works
Houštěk, J., Cannon, B., & Lindberg, O. (1975) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1975.tb04107.x · Cited by 77 · see citing works
Hydrogen peroxide production by mitochondria may be a biomarker of aging
Sohal, R. S. (1991) · Mechanisms of Ageing and Development · doi:10.1016/0047-6374(91)90130-r · Cited by 71 · see citing works
Cussenot, O., Berthon, P., Cochand-Priollet, B., et al. (1994) · Experimental Cell Research · doi:10.1006/excr.1994.1236 · Cited by 65 · see citing works
Cole, E., Lepp, C. A., Holohan, P. D., & Fondy, T. P. (1978) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)34463-0 · Cited by 50 · see citing works
Biochemistry of brown fat and liver of cold-acclimated hamsters
Chaffee, R. R. J., Allen, J. R., Cassuto, Y., et al. (1964) · American Journal of Physiology-Legacy Content · doi:10.1152/ajplegacy.1964.207.6.1211 · Cited by 50 · see citing works
High activity of α-glycerophosphate oxidation by human placental mitochondria
Świerczyński, J., Ścisłowski, P. W. D., & Aleksandrowicz, Z. (1976) · Biochimica et Biophysica Acta (BBA) - Enzymology · doi:10.1016/0005-2744(76)90028-0 · Cited by 49 · see citing works
Rasschaert, J., & Malaisse, W. J. (1991) · Biochemical Journal · doi:10.1042/bj2780335 · Cited by 45 · see citing works
Müller, S. P., & Seitz, H. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10581 · Cited by 42 · see citing works
Weitzel, J. M., Kutz, S., Radtke, C., et al. (2001) · European Journal of Biochemistry · doi:10.1046/j.1432-1327.2001.02332.x · Cited by 41 · see citing works
Activities of mitochondrial oxidative phosphorylation enzymes in cultured amniocytes
Chowdhury, S. R., Drahota, Z., Floryk, D., Calda, P., & Houštěk, J. (2000) · Clinica Chimica Acta · doi:10.1016/s0009-8981(00)00300-4 · Cited by 38 · see citing works
Self-citationMitochondria from brown adipose tissue
Aldridge, W. N., & Street, B. W. (1968) · Biochemical Journal · doi:10.1042/bj1070315 · Cited by 35 · see citing works
Ishihara, H., Nakazaki, M., Kanegae, Y., et al. (1996) · Diabetes · doi:10.2337/diab.45.9.1238 · Cited by 34 · see citing works
α-Glycerophosphate Dehydrogenase Activity in Rat Spermatozoa
Schenkman, J. B., Richert, D. A., & Westerfeld, W. W. (1965) · Endocrinology · doi:10.1210/endo-76-6-1055 · Cited by 33 · see citing works
Rauchová, H., Fato, R., Drahota, Z., & Lenaz, G. (1997) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1997.0150 · Cited by 30 · see citing works
Weitzel, J. M., Shiryaeva, N. B., Middendorff, R., et al. (2003) · Biology of Reproduction · doi:10.1095/biolreprod.102.008540 · Cited by 30 · see citing works
MacDonald, M. J., Warner, T. F. C. S., & Mertz, R. J. (1990) · PubMed · Cited by 28 · see citing works
Developmental Regulation of the α-Glycerophosphate Shuttle in Porcine Myocardium
SCHOLZ, T. D., Koppenhafer, S. L., TenEyck, C. J., et al. (1997) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1997.0394 · Cited by 24 · see citing works
COTTINGHAM, I. R., & RAGAN, C. I. (1980) · Biochemical Journal · doi:10.1042/bj1920019 · Cited by 19 · see citing works
Glycerophosphate-dependent hydrogen peroxide production by rat liver mitochondria.
Ješina, P., Kholová, D., Bolehovská, R., et al. (2004) · Physiological Research · doi:10.33549/physiolres.930449 · Cited by 18 · see citing works
Bobyleva, V., Pazienza, T. L., Muscatello, U., Kneer, N. M., & Lardy, H. A. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.2000.1942 · Cited by 15 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The emerging hallmarks of cancer metabolism
Pavlova, N. N., & Thompson, C. B. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2015.12.006 · Cited by 5,926 · see citing works
Rigoulet, M., Yoboue, E. D., & Devin, A. (2011) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3363 · Cited by 394 · see citing works
Inhibition of mitochondrial glycerol-3-phosphate dehydrogenase by α-tocopheryl succinate
Rauchová, H., Vokurková, M., & Drahota, Z. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.06.010 · Cited by 14 · see citing works
- Authors
- Chowdhury, S. K. R., Gemin, A., & Singh, G.
- Affiliations
- Juravinski Cancer Centre (CA)
- Corresponding author
- Singh, Gurmit
- ORCID
- Singh, Gurmit
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2005-08
- Volume
- 333
- Issue
- 4
- Pages
- 1139-1145
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2092715210
- Cited by
- 83
- References
- 38
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 4 · 2020: 1 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 3 · 2014: 4 · 2013: 4 · 2012: 6
- FWCI
- 2.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research
- Congressionally Directed Medical Research Programs
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- prostate cancer, reactive oxygen species, glycolysis, electron transport chain, NADH reoxidation, electron leakage, cancer metabolism
- MeSH terms
- Enzyme Activation, Glycerolphosphate Dehydrogenase, Glycerophosphates, Glycolysis, Humans, Male, Mitochondria, Oxygen, Oxygen Consumption, Prostatic Neoplasms, Reactive Oxygen Species, Cell Line, Tumor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review