Sodium pyruvate protects against H2O2 mediated apoptosis in human neuroblastoma cell line-SK-N-MC

Jagtap, Jayashree C.; Chandele, Anmol; Chopde, B.A.; Shastry, Padma

doi:10.1016/s0891-0618(03)00037-1

Cited by 50 publications

(31 citation statements)

References 28 publications

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“…First, pyruvate exerts significant protection of neuronally derived SK-N-SH cells against H 2 O 2 -induced oxidative stress in both cotreatment as well as delayed treatment protocols. Concordant with reports of other investigators, the cytoprotective effects of pyruvate are concentration-dependent, and are afforded by physiological (high μM) to pharmacological (low mM) concentrations [13,26]. The therapeutic window of pyruvate administration extends up to 2 hr after H 2 O 2 insult, suggesting pyruvate protects cells by mechanisms other than its direct nonenzymatic reaction with H 2 O 2 .…”

Section: Discussionsupporting

confidence: 83%

Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells

et al. 2007

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Oxidative stress is implicated in neurodegenerative diseases including stroke, Alzheimer's disease and Parkinson's disease, and has been extensively studied as a potential target for therapeutic intervention. Pyruvate, a natural metabolic intermediate and energy substrate, exerts antioxidant effects in brain and other tissues susceptible to oxidative stress. We tested the protective effects of pyruvate on hydrogen peroxide (H 2 O 2 ) toxicity in human neuroblastoma SK-N-SH cells and the mechanisms underlying its protection. Hydrogen peroxide insult resulted in 85% cell death, but cotreatment with pyruvate dose-dependently attenuated cell death. At concentrations of ≥ 1 mM, pyruvate totally blocked the cytotoxic effects of H 2 O 2 . Pyruvate exerted its protective effects even when its administration was delayed up to 2 hr after H 2 O 2 insult. As a scavenger of reactive oxygen species (ROS), pyruvate dose-dependently attenuated H 2 O 2 -induced ROS formation, assessed from 2,7-dichlorofluorescein diacetate fluorescence. Furthermore, pyruvate suppressed superoxide production by submitochondrial particles, and attenuated oxidative stress-induced collapse of the mitochondrial membrane potential. Collectively, these results suggest pyruvate protects neuronal cells through its antioxidant actions on mitochondria.

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Section: Discussionsupporting

confidence: 83%

Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells

et al. 2007

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“…The transient expression of P-gp in multicellular tumor spheroids may be due to the anti-oxidant properties of pyruvate which was elevated in small tumor spheroids and exchanged against lactate with increasing size of spheroids and time of cell culture. The antioxidant properties of pyruvate have been recently demonstrated to protect human neuroblastoma cells against hydrogen peroxidemediated apoptosis [Jagtap et al, 2003] and to protect mitochondria from oxidative stress [Wang et al, 2007]. Via its anti-oxidative properties pyruvate may enable the tumor cells to survive in a proapoptotic, hypoxic microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Glycolytic pyruvate regulates P‐Glycoprotein expression in multicellular tumor spheroids via modulation of the intracellular redox state

Wartenberg

Richter

Datchev

et al. 2009

J of Cellular Biochemistry

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To investigate the effect of glycolysis and the tissue redox state on P-gp expression in multicellular tumor spheroids derived from prostate adenocarcinoma cells (DU-145), glioma cells (Gli36), and the human cervix carcinoma cell line KB-3-1 transfected with a P-gp-EGFP fusion gene that allows monitoring of P-gp expression in living cells. During cell culture of DU-145, Gli36, and KB-3-1 tumor spheroids P-gp expression was observed as well as increased lactate and decreased pyruvate levels and expression of glycolytic enzymes. Inhibition of glycolysis for 24 h by either iodoacetate (IA) or 2-deoxy-D-glucose (2-DDG) downregulated P-gp expression which was reversed upon coincubation with the radical scavenger ebselen as shown by semi-quantitative immunohistochemisty in DU-145 and Gli36 tumor spheroids, and by EGFP fluorescence in KB-3-1 tumor spheroids. Consequently endogenous ROS generation in DU-145 tumor spheroids was increased in the presence of either IA or 2-DDG, which was abolished upon coincubation with ebselen. Exogenous addition of pyruvate significantly reduced ROS generation, increased P-gp expression as well as efflux of the P-gp substrate doxorubicin. Doxorubicin transport was significantly blunted by 2-DDG and IA, indicating that inhibition of glycolysis reversed the multidrug resistance phenotype. In summary our data demonstrate that P-gp expression in tumor spheroids is closely related to the glycolytic metabolism of tumor cells and can be downregulated by glycolysis inhibitors via mechanisms that involve changes in the cellular redox state.

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“…A possible function for pyruvate in protecting embryos against oxidative stress has been suggested (O'Fallon & Wright 1995), and it was reported that pyruvate prevented peroxide-induced injury of in vitro cultured bovine embryos (Morales et al 1999) and protected human spermatozoa against the effect of ROS (de Lamirande & Gagnon 1992). Furthermore, it has been demonstrated that pyruvate prevents ROSinduced apoptosis in various types of somatic cells (Ramakrishnan et al 1998, Kang et al 2001, Mongan et al 2002, Jagtap et al 2003), mainly by maintaining the level of GSH (Mongan et al 2002), increasing the ratio of anti-apoptotic molecules BCL2 or BCL2L1 to pro-apoptotic molecule BAX (Mongan et al 2002 and by inhibiting the activation of caspase-3 (Mongan et al 2002, Jagtap et al 2003, Lee et al 2004). …”

Section: N Liu Y-g Wu and Othersmentioning

confidence: 99%

Pyruvate prevents aging of mouse oocytes

Liu

Wu²,

Lan³

et al. 2009

Reproduction

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Inhibiting oocyte aging is important not only for healthy reproduction but also for the success of assisted reproduction techniques. Although our previous studies showed that cumulus cells accelerated aging of mouse oocytes, the underlying mechanism is unknown. The objective of this paper was to study the effects of pyruvate and cumulus cells on mouse oocyte aging. Freshly ovulated mouse cumulus-oocyte complexes (COCs) or cumulus-denuded oocytes (DOs) were cultured in Chatot-Ziomek-Bavister (CZB) medium or COC-conditioned CZB medium supplemented with different concentrations of pyruvate before being examined for aging signs and developmental potential. Pyruvate supplementation to CZB medium decreased rates of ethanol-induced activation in both COCs and DOs by maintaining their maturation-promoting factor activities, but more pyruvate was needed for COCs than for DOs. Addition of pyruvate to the COC-conditioned CZB also alleviated aging of DOs. Observations on cortical granules, level of BCL2 proteins, histone acetylation, intracellular concentration of glutathione, and embryo development all confirmed that pyruvate supplementation inhibited aging of mouse oocytes. It is concluded that the aging of mouse oocytes, facilitated by culture in COCs, can be partially prevented by the addition of pyruvate to the culture medium.

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Sodium pyruvate protects against H2O2 mediated apoptosis in human neuroblastoma cell line-SK-N-MC

Cited by 50 publications

References 28 publications

Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells

Pyruvate protects mitochondria from oxidative stress in human neuroblastoma SK-N-SH cells

Glycolytic pyruvate regulates P‐Glycoprotein expression in multicellular tumor spheroids via modulation of the intracellular redox state

Pyruvate prevents aging of mouse oocytes

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