Curcumin prevents methylglyoxal‐induced oxidative stress and apoptosis in mouse embryonic stem cells and blastocysts

Hsuuw, Yan‐Der; Chang, Chen-Kang; Chan, Wen‐Hsiung; Yu, Jau‐Song

doi:10.1002/jcp.20408

Cited by 125 publications

(116 citation statements)

References 48 publications

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“…Severe dicarbonyl stress also induces decreased cell growth and viability -as we and others have found previously in ESCs, other cell types, mouse oocytes, fertilization, and fetal development [52][53][54]. Mild dicarbonyl stress was induced by mESC culture in 3% oxygenthrough down regulation of Glo1 expression and increased anaerobic glycolysis with increased flux of formation of MG.…”

Section: Discussionsupporting

confidence: 71%

Reappraisal of putative glyoxalase 1-deficient mouse and dicarbonyl stress on embryonic stem cellsin vitro

Shafie

Xue

Barker

et al. 2016

Biochemical Journal

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Glyoxalase 1 (Glo1) is a cytoplasmic enzyme with a cytoprotective function linked to metabolism of the cytotoxic side product of glycolysis, methylglyoxal (MG). It prevents dicarbonyl stress — the abnormal accumulation of reactive dicarbonyl metabolites, increasing protein and DNA damage. Increased Glo1 expression delays ageing and suppresses carcinogenesis, insulin resistance, cardiovascular disease and vascular complications of diabetes and renal failure. Surprisingly, gene trapping by the International Mouse Knockout Consortium (IMKC) to generate putative Glo1 knockout mice produced a mouse line with the phenotype characterised as normal and healthy. Here, we show that gene trapping mutation was successful, but the presence of Glo1 gene duplication, probably in the embryonic stem cells (ESCs) before gene trapping, maintained wild-type levels of Glo1 expression and activity and sustained the healthy phenotype. In further investigation of the consequences of dicarbonyl stress in ESCs, we found that prolonged exposure of mouse ESCs in culture to high concentrations of MG and/or hypoxia led to low-level increase in Glo1 copy number. In clinical translation, we found a high prevalence of low-level GLO1 copy number increase in renal failure where there is severe dicarbonyl stress. In conclusion, the IMKC Glo1 mutant mouse is not deficient in Glo1 expression through duplication of the Glo1 wild-type allele. Dicarbonyl stress and/or hypoxia induces low-level copy number alternation in ESCs. Similar processes may drive rare GLO1 duplication in health and disease.

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Section: Discussionsupporting

confidence: 71%

Reappraisal of putative glyoxalase 1-deficient mouse and dicarbonyl stress on embryonic stem cellsin vitro

Shafie

Xue

Barker

et al. 2016

Biochemical Journal

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“…have not yet been clearly defined, studies have shown that caspase activation, MMP (mitochondrial membrane potential) changes and JNK (c-Jun N-terminal kinase) activation are critical for the mitochondria-dependent apoptotic pathway [9,14]. In addition, previous studies have shown that some apoptotic stimuli trigger heat-shock responses, such as activation of the HSPs (heat-shock proteins), which are molecular chaperones that rescue damaged proteins by facilitating their refolding [15,16].…”

Section: Introductionmentioning

confidence: 99%

“…However, apoptotic processes do not occur prior to the blastocyst stage during normal mouse embryonic development [8], and induction of apoptosis during the early stages of embryogenesis (i.e. by exposure to a teratogen) has been shown to cause embryonic developmental injury [9,10]. Many of the chemical and physical treatments that induce apoptosis stimulate oxidative stress via generation of ROS (reactive oxygen species) [9,[11][12][13], suggesting a close relationship between oxidative stress and apoptosis.…”

Section: Introductionmentioning

confidence: 99%

“…by exposure to a teratogen) has been shown to cause embryonic developmental injury [9,10]. Many of the chemical and physical treatments that induce apoptosis stimulate oxidative stress via generation of ROS (reactive oxygen species) [9,[11][12][13], suggesting a close relationship between oxidative stress and apoptosis. While the precise molecular mechanisms underlying apoptosis…”

Section: Introductionmentioning

confidence: 99%

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Citrinin induces apoptosis via a mitochondria-dependent pathway and inhibition of survival signals in embryonic stem cells, and causes developmental injury in blastocysts

Chan

2007

Biochemical Journal

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The mycotoxin CTN (citrinin), a natural contaminant in foodstuffs and animal feeds, has cytotoxic and genotoxic effects on various mammalian cells. CTN is known to cause cell injury, including apoptosis, but the precise regulatory mechanisms of CTN action, particularly in stem cells and embryos, are currently unclear. In the present paper, I report that CTN has cytotoxic effects on mouse embryonic stem cells and blastocysts, and is associated with defects in their subsequent development, both in vitro and in vivo. Experiments in embryonic stem cells (ESC-B5) showed that CTN induces apoptosis via ROS (reactive oxygen species) generation, increased Bax/Bcl-2 ratio, loss of MMP (mitochondrial membrane potential), induction of cytochrome c release, and activation of caspase 3. In this model, CTN triggers cell death via inactivation of the HSP90 [a 90 kDa isoform of the HSP (heat-shock protein) family proteins]/multichaperone complex and subsequent degradation of Ras and Raf-1, further inhibiting anti-apoptotic processes, such as the Ras → ERK (extracellular-signal-regulated kinase) signal transduction pathway. In addition, CTN causes early developmental injury in mouse ESCs and blastocysts in vitro. Lastly, using an in vivo mouse model, I show that consumption of drinking water containing 10 µM CTN results in blastocyst apoptosis and early embryonic developmental injury. Collectively, these findings show for the first time that CTN induces ROS and mitochondria-dependent apoptotic processes, inhibits Ras → ERK survival signalling via inactivation of the HSP90/multichaperone complex, and causes developmental injury in vivo.

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“…It has been reported that transforming growth factor ␣ protects ICM from apoptosis [3,4]. Cultured mouse embryonic stem (mES) cells derived from ICM undergo apoptosis when subjected to prolonged hypoxia or methylglyoxal-induced oxidative stress [5,6]. However, little is known about the endogenous protective mechanism.…”

Section: Introductionmentioning

confidence: 99%

Cyclooxygenase-2-Derived Prostaglandin E2 Protects Mouse Embryonic Stem Cells from Apoptosis

et al. 2007

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Little is known about prostaglandin synthesis and function in embryonic stem cells. We postulated that mouse embryonic stem (mES) cells possess enzymes to synthesize protective prostaglandins. Compared with differentiated adult cells, mES cells were less susceptible to H 2 O 2 -induced apoptosis. However, their apoptosis was enhanced by indomethacin or SC-236, a selective inhibitor of cyclooxygenase (COX)-2. Analysis of COX pathway enzymes by Western blotting revealed expression of COX-2 and cytosolic and microsomal prostaglandin E 2 (PGE 2 ) synthases. COX-1 and prostacyclin (PGI 2 ) synthases were undetectable. mES cells produced PGE 2 but not PGI 2 . Importantly, PGE 2 rescued mES cells from apoptosis. To elucidate the signaling mechanism by which PGE 2 inhibits apoptosis, we analyzed E-type prostaglandin (EP) receptors by Western blots. All EP isoforms were detected except EP4. Butaprost, a specific EP2 agonist, rescued mES cells from apoptosis, whereas sulprostone, an EP1/EP3 agonist, had no effect, suggesting selective interaction of PGE 2 with EP2. The antiapoptotic effect of PGE 2 was abrogated by Ly-294002 or wortmannin but not H-89 or a specific inhibitor of protein kinase A, suggesting signaling via phosphatidylinositol-3 kinase (PI-3K). Akt was constitutively active in mES cells, which were inhibited by indomethacin and rescued by PGE 2 . The rescuing effect of PGE 2 was abrogated by Ly-294002. These results indicate that mES cells constitutively express COX-2 and PGE synthases and produce PGE 2 , which confers resistance to apoptosis via EP2-mediated activation of PI-3K to the Akt pathway.

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Curcumin prevents methylglyoxal‐induced oxidative stress and apoptosis in mouse embryonic stem cells and blastocysts

Cited by 125 publications

References 48 publications

Reappraisal of putative glyoxalase 1-deficient mouse and dicarbonyl stress on embryonic stem cellsin vitro

Reappraisal of putative glyoxalase 1-deficient mouse and dicarbonyl stress on embryonic stem cellsin vitro

Citrinin induces apoptosis via a mitochondria-dependent pathway and inhibition of survival signals in embryonic stem cells, and causes developmental injury in blastocysts

Cyclooxygenase-2-Derived Prostaglandin E2 Protects Mouse Embryonic Stem Cells from Apoptosis

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