Eicosatetraynoic and eicosatriynoic acids, lipoxygenase  inhibitors, block meiosis via antioxidant action

Takami, Masashi; Preston, Sandra L.; Behrman, Harold R.

doi:10.1152/ajpcell.2000.278.4.c646

Cited by 31 publications

(15 citation statements)

References 22 publications

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“…These results corroborate previous observations that exogenous supplementation of H 2 O 2 triggers meiotic resumption, 20,38 and generation of ROS is beneficial for increasing the developmental potential of oocytes under in vitro culture conditions, 38 while antioxidants reversibly inhibit meiotic resumption from diplotene arrest in vitro . 19,22,23 …”

Section: Discussionmentioning

confidence: 99%

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A Moderate Increase of Hydrogen Peroxide Level Is Beneficial for Spontaneous Resumption of Meiosis from Diplotene Arrest in Rat Oocytes CulturedIn Vitro

Pandey

Chaube

2014

BioResearch Open Access

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Hydrogen peroxide (H2O2) acts as a signaling molecule and modulates various aspects of cell functions in a wide variety of cells including mammalian germ cells. We examined whether a decreased level of intra-oocyte cyclic 3′,5′-adenosine monophosphate (cAMP) leads to accumulation of H2O2, and if so, whether a moderate increase of H2O2 inactivates maturation promoting factor (MPF) during spontaneous resumption of meiosis in rat oocytes cultured in vitro. Removal of cumulus cells and culture of denuded oocytes in vitro significantly decreased oocyte cAMP level and led to spontaneous meiotic resumption from diplotene arrest. The reduced oocyte cAMP level was associated with an increased oocyte H2O2 level and reduced catalase activity. Exogenous supplementation of H2O2 induced meiotic resumption from diplotene arrest in a concentration- and time-dependent manner in oocytes treated with 0.1 mM of 3-isobutyl-1-methylxanthine, while dibutyryl-cAMP and 3-t-butyl-4-hydroxyanisole inhibited the stimulatory effect of exogenous H2O2. The increased intra-oocyte H2O2 level induced Thr-14/Tyr-15 phosphorylation of CDK1, while Thr-161 phosphorylated CDK1 and cyclin B1 levels were reduced significantly. These results suggest that a decreased level of intra-oocyte cAMP is associated with an increased level of H2O2. The increased level of H2O2 was associated with high phosphorylation of Thr-14/Tyr-15 and dephosphorylation of the Thr-161 residue of CDK1 and reduced the cyclin B1 level, which eventually inactivated MPF. The MPF inactivation triggered spontaneous resumption of meiosis from diplotene arrest in rat oocytes cultured in vitro.

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Section: Discussionmentioning

confidence: 99%

“…8,19–21 On the other hand, antioxidants inhibit meiotic resumption from diplotene arrest in mammalian oocytes cultured in vitro . 22,23 …”

Section: Introductionmentioning

confidence: 99%

A Moderate Increase of Hydrogen Peroxide Level Is Beneficial for Spontaneous Resumption of Meiosis from Diplotene Arrest in Rat Oocytes CulturedIn Vitro

Pandey

Chaube

2014

BioResearch Open Access

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“…The pan-LOX inhibitor NDGA also effectively blocked fenretinideinduced free radicals in SH-SY5Y cells (DCFDA fluorescence, arbitrary units AE SD, n ¼ 3: control, 5.17 AE 0.06; 50 mM NDGA, 13.02 AE 1.57; 10 mM fenretinide, 34.5 AE 2.84; 50 mM NDGA þ 10 mM fenretinide, 9.4 AE 0.63); however, it was not possible to measure an effect of NDGA on fenretinide-induced apoptosis as this agent produced high levels of cell death alone (data not shown). Apoptosis of SH-SY5Y and HTLA 230 cells, and the induction of ROS in SH-SY5Y cells was also blocked by baicalein, a specific inhibitor of 12-LOX [Huang et al, 1994], and by ETI which inhibits 5-and 12-LOX at an IC 50 of 20 mM [Takami et al, 2000] (Figs. 3-5).…”

Section: Loxs Mediate Fenretinide-induced Ros and Apoptosis Of Neurobmentioning

confidence: 92%

“…To investigate the role of LOX enzymes in mediating the effects of fenretinide, we used a range of LOX inhibitors, at appropriate concentrations to prevent cross specificity, to treat SH-SY5Y and HTLA 230 cells 2 h prior to addition of fenretinide. Two pan-LOX inhibitors, esculetin, which blocks activity by binding to LOX [Moore et al, 1991], and ETYA, which blocks LOX activity by competing with AA [Takami et al, 2000], did not induce ROS or apoptosis on their own but were effective in blocking fenretinide-induced ROS and apoptosis of SY-SY5Y cells (Figs. 3-4).…”

Section: Loxs Mediate Fenretinide-induced Ros and Apoptosis Of Neurobmentioning

confidence: 99%

Mechanisms of free‐radical induction in relation to fenretinide‐induced apoptosis of neuroblastoma

Lovat

Ranalli

Corazzari

et al. 2003

J of Cellular Biochemistry

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The mechanisms of fenretinide-induced cell death of neuroblastoma cells are complex, involving signaling pathways mediated by free radicals or reactive oxygen species (ROS). The aim of this study was to identify mechanisms generating ROS and apoptosis of neuroblastoma cells in response to fenretinide. Fenretinide-induced ROS or apoptosis of SH-SY5Y or HTLA 230 neuroblastoma cells were not blocked by Nitro l-argenine methyl ester (l-NAME), an inhibitor of nitric oxide synthase. Flavoprotein-dependent superoxide-producing enzymes such as NADPH oxidase were also not involved in fenretinide-induced apoptosis or ROS generation. Similarly, ketoconazole, a cytochrome P450 inhibitor, and inhibitors of cyclooxygenase (COX) were also ineffective. In contrast, inhibition of phospholipase A(2) or lipoxygenases (LOX) blocked the induction of ROS and apoptosis in response to fenretinide. Using specific inhibitors of LOX, blocking 12-LOX but not 5- or 15-LOX inhibited both fenretinide-induced ROS and apoptosis. The effects of eicosatriynoic acid, a specific 12-LOX inhibitor, were reversed by the addition of the 12-LOX products, 12 (S)-hydroperoxyeicosatetraenoic acid and 12 (S)-hydroxyeicosatetraenoic acid. The targeting of 12-LOX in neuroblastoma cells may thus be a novel pathway for the development of drugs inducing apoptosis of neuroblastoma with improved tumor specificity.

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“…5 Further, exogenous exposure of antioxidants is reported to inhibit meiotic resumption in immature oocytes cultured in vitro. [6][7][8] On the other hand, H 2 O 2 (10.0-100.0 µM) is reported to induce cell cycle arrest in various somatic cell types. [9][10][11] The thiol oxidation and H 2 O 2 (175.0 µM) are reported to induce developmental arrest in mouse embryo, 12,13 while antioxidants reduce oxidative stress damage in oocyte and embryo and improve their developmental abilities.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen peroxide modulates meiotic cell cycle and induces morphological features characteristic of apoptosis in rat oocytes cultured in vitro

et al. 2005

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Hydrogen peroxide (H2O2) is known to induce cell cycle arrest and apoptosis in various somatic cell types cultured in vitro. We hypothesize that this reactive oxygen species (ROS) could modulate cell cycle and induce morphological features characteristics of apoptosis in oocytes cultured in vitro. To test this hypothesis, immature and mature oocytes were cultured in medium containing various doses of H2O2 with or without caspase-3 inhibitor for various times. The treatment of H2O2 induced germinal vesicle break down (GVBD) in all immature oocytes followed by initiation of shrinkage. Some of immature oocytes (but not mature oocytes) also showed membrane blebbing. On the other hand, H2O2 treatment inhibited first polar body emission in mature oocytes just prior to initiation of shrinkage. The cytoplasmic granulation and fragmentation into apoptotic bodies were observed in mature oocytes during later stages of H2O2 treatment. The shrinkage was induced by H2O2 in a dose- and time-dependent manner in both immature and mature oocytes. Although, H2O2-induced degeneration was observed in both immature and mature oocytes after 2.0 hrs of treatment, immature oocytes were more susceptible to undergo quick shrinkage, membrane blebbing and degeneration. Co-addition of caspase-3 inhibitor prevented shrinkage and degeneration of both immature and mature oocytes except membrane blebbing that was observed at higher doses of H2O2 after 1.0 hr of culture. Treatment of H2O2 induced bax protein expression (3 times), DNA fragmentation and caspase-3 activity (2.5 times) in oocytes undergoing morphological apoptotic changes. These findings clearly suggest that H2O2 induced GVBD in immature oocytes, inhibited first polar body extrusion in mature oocytes prior to initiation of morphological changes characteristic of apoptosis such as shrinkage, membrane blebbing and cytoplasmic fragmentation prior to degeneration.

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Eicosatetraynoic and eicosatriynoic acids, lipoxygenase inhibitors, block meiosis via antioxidant action

Cited by 31 publications

References 22 publications

A Moderate Increase of Hydrogen Peroxide Level Is Beneficial for Spontaneous Resumption of Meiosis from Diplotene Arrest in Rat Oocytes CulturedIn Vitro

A Moderate Increase of Hydrogen Peroxide Level Is Beneficial for Spontaneous Resumption of Meiosis from Diplotene Arrest in Rat Oocytes CulturedIn Vitro

Mechanisms of free‐radical induction in relation to fenretinide‐induced apoptosis of neuroblastoma

Hydrogen peroxide modulates meiotic cell cycle and induces morphological features characteristic of apoptosis in rat oocytes cultured in vitro

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