High activity of mitochondrial glycerophosphate dehydrogenase and glycerophosphate-dependent ROS production in prostate cancer cell lines

Chowdhury, Subir; Gemin, Adam; Singh, Gurmit

doi:10.1016/j.bbrc.2005.06.017

Cited by 74 publications

(58 citation statements)

References 37 publications

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“…therein) or in cerebellar granule cell homogenates (25 and refs. therein), in agreement with (34,35) we conclude that in prostate mitochondria energy production from both glycolitic substrates, such as L-LAC, and SUC is very poor. These findings are consistent with a previous report (18) where fatty acid oxidation was reported as a dominant bioenergetic pathway in prostate cancer.…”

Section: Discussionsupporting

confidence: 88%

L-lactate metabolism can occur in normal and cancer prostate cells via the novel mitochondrial L-lactate dehydrogenase

Bari

Chieppa²,

Marra³

et al. 2010

Int J Oncol

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Abstract. Both normal (PTN1A) and cancer (PC3) prostate cells produce high levels of L-lactate because of a low energy supply via the citric cycle and oxidative phosphorylation. Since some mammalian mitochondria possess a mitochondrial L-lactate dehydrogenase (mLDH), we investigated whether prostate cells can take up L-lactate and metabolize it in the mitochondria. We report here that externally added L-lactate can enter both normal and cancer cells and mitochondria, as shown by both the oxygen consumption and by the increase in fluorescence of NAD(P)H which occur as a result of L-lactate addition. In both cell types L-lactate enters mitochondria in a carrier-mediated manner, as shown by the inhibition of swelling measurements due to the non-penetrant thiol reagent mersalyl. An L-lactate dehydrogenase exists in mitochondria of both cell types located in the inner compartment, as shown by kinetic investigation and by immunological analysis. The mLDHs proved to differ from the cytosolic enzymes (which themselves differ from one another) as functionally investigated with respect to kinetic features and pH profile. Normal and cancer cells were found to differ from one another with respect to mLDH protein level and activity, being the enzyme more highly expressed and of higher activity in PC3 cells. Moreover, the kinetic features and pH profiles of the PC3 mLDH also differ from those of the PNT1A enzyme, this suggesting the occurrence of separate isoenzymes.

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Section: Discussionsupporting

confidence: 88%

L-lactate metabolism can occur in normal and cancer prostate cells via the novel mitochondrial L-lactate dehydrogenase

Bari

Chieppa²,

Marra³

et al. 2010

Int J Oncol

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“…Androgens maintain male muscle mass (10a, 26, 50) and induce muscle cellular gene expression. During prostate cancer progression, metabolism shifts toward cytosolic glycolysis (1,12). The increased production of lactate that occurs during prostate cancer progression (5, 46) is predicted to inhibit SIRT1 and thereby enhance AR function.…”

Section: Discussionmentioning

confidence: 99%

Hormonal Control of Androgen Receptor Function through SIRT1

Liu

Sauve

et al. 2006

Molecular and Cellular Biology

213

209

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The NAD-dependent histone deacetylase Sir2 plays a key role in connecting cellular metabolism with gene silencing and aging. The androgen receptor (AR) is a ligand-regulated modular nuclear receptor governing prostate cancer cellular proliferation, differentiation, and apoptosis in response to androgens, including dihydrotestosterone (DHT). Here, SIRT1 antagonists induce endogenous AR expression and enhance DHTmediated AR expression. SIRT1 binds and deacetylates the AR at a conserved lysine motif. Human SIRT1 (hSIRT1) repression of DHT-induced AR signaling requires the NAD-dependent catalytic function of hSIRT1 and the AR lysine residues deacetylated by SIRT1. SIRT1 inhibited coactivator-induced interactions between the AR amino and carboxyl termini. DHT-induced prostate cancer cellular contact-independent growth is also blocked by SIRT1, providing a direct functional link between the AR, which is a critical determinant of progression of human prostate cancer, and the sirtuins.

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“…This could indicate ROS release at complex I (via RET) but also at complex III (Chowdhury et al 2005;Drose and Brandt 2012;Tretter et al 2007). Of note, upon TCR triggering, complex III seems to be activated by a stable modification in a PKC-dependent manner (Kaminski et al 2012b).…”

Section: The Enzymatic Sources Of the Oxidative Signalmentioning

confidence: 99%

“…Activated GPD2 directly reduces ubiquinone and releases ROS either at the complex I via RET or itself. Moreover, since complex III and IV inhibitors enhance GPD2-dependent ROS production (Chowdhury et al 2005;Lambert and Brand 2009;Miwa et al 2003;Tretter et al 2007), complex III involvement is also possible. Therefore, GPD2 plays a major role for T-cell activationinduced ROS release by connecting enhanced glycolysis with hyper-reduction of the mitochondrial respiratory chain (Fig.…”

Section: The Enzymatic Sources Of the Oxidative Signalmentioning

confidence: 99%

“…For example, exceptionally high activity of mitochondrial GPD2 was reported for insulinomas and carcinoid tumors (MacDonald et al 1990) as well as for prostate cancer, where it was indicative for high ROS generation (Chowdhury et al 2005(Chowdhury et al , 2007. K-Ras-induced transformation results in up-regulation of ADPGK expression, increase in aerobic glycolytic rate and high mitochondrial ROS release (Gaglio et al 2011;Hu et al 2012;Weinberg et al 2010).…”

Section: Cancermentioning

confidence: 99%

See 1 more Smart Citation

Mitochondria as Oxidative Signaling Organelles in T-cell Activation: Physiological Role and Pathological Implications

Kamiński

Röth

Krammer

et al. 2013

Arch. Immunol. Ther. Exp.

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High activity of mitochondrial glycerophosphate dehydrogenase and glycerophosphate-dependent ROS production in prostate cancer cell lines

Cited by 74 publications

References 37 publications

L-lactate metabolism can occur in normal and cancer prostate cells via the novel mitochondrial L-lactate dehydrogenase

L-lactate metabolism can occur in normal and cancer prostate cells via the novel mitochondrial L-lactate dehydrogenase

Hormonal Control of Androgen Receptor Function through SIRT1

Mitochondria as Oxidative Signaling Organelles in T-cell Activation: Physiological Role and Pathological Implications

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