Autophagy inhibition through PI3K/Akt increases apoptosis by sodium selenite in NB4 cells

Ren, Yu; Huang, Fang; Liu, Yuan; Yang, Yang; Jiang, Qian; Xu, Caimin

doi:10.5483/bmbrep.2009.42.9.599

Cited by 73 publications

(57 citation statements)

References 28 publications

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“…Rapamycin, which irreversibly inhibits mTORC1, leading to the sustained inhibition of cell growth, is known to induce autophagy [43]. Taken together, these results demonstrate that treatment of embryos with 3-MA or rapamycin alters the expression of autophagy-related genes (Atg5, Beclin1 and Lc3), which is consistent with the modulation of autophagy by these drugs in other cell types [26,44]. Furthermore, this modulation of autophagy may influence early embryonic development.…”

supporting

confidence: 74%

Autophagy Influences Maternal mRNA Degradation and Apoptosis in Porcine Parthenotes Developing <i>In Vitro</i>

Shen

Lee

et al. 2012

Journal of Reproduction and Development

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Abstract. Autophagy, an essential process for cellular maintenance, cell viability, and development, is the bulk degradation of proteins and organelles. This study investigated the expression levels of autophagy-related genes and the effect of 3-methyladenine (3-MA, an autophagy inhibitor) or rapamycin (an autophagy inducer) on maternal gene degradation and apoptosis in porcine parthenotes developing in vitro. LC3, which is essential for the formation of autophagosomes, was widely expressed in porcine parthenotes. High levels of autophagy-related genes, Atg5, Beclin1 and Lc3 transcripts were expressed in the 1-cell (1C) stage and gradually decreased through the 2-cell (2C) to blastocyst stages. The mRNA expression of Gdf9, c-mos and cyclin B maintained high levels in 2C and 4-cell (4C) embryos treated with 3-MA compared with the control. The Bmp15 and cyclin B mRNA levels were significantly reduced in embryos treated with rapamycin compared with the control. These results suggest that autophagy influences the degradation of these maternal genes. Furthermore, 3-MA-treated embryos exhibited significantly reduced developmental rates, decreased total cell numbers and increased rates of apoptosis. Expression of Atg5, Beclin1 and Lc3 and synthesis of LC3 protein were significantly reduced at the blastocyst stage. Although rapamycin treatment did not affect the developmental rate, it decreased the cell number and increased the rate of apoptosis, and the expression of Atg5, Beclin1 and Lc3 and LC3 protein synthesis were increased. Finally, blastocysts derived following treatment with 3-MA or rapamycin exhibited significantly decreased expression of selected transcription factors, including Pou5f1, Sox2 and Nanog. In conclusion, our results demonstrate that autophagy influences maternal mRNA degradation and apoptosis at the blastocyst stage and suggest that autophagy plays an important role in early embryo development in the pig. Key words: Apoptosis, Autophagy, LC3, Maternal gene, 3-MA, Rapamycin (J. Reprod. Dev. 58: [576][577][578][579][580][581][582][583][584] 2012) A utophagy is an intracellular, bulk degradation process in which a portion of the cytoplasm is sequestered in an autophagosome and subsequently degraded upon fusion with a lysosome [1][2][3]. Autophagy plays a critical role during fertilization [4] and an essential role in differentiation and development, as well as in the cellular response to stress. Our previous study was the first to report that mitochondrial stress influences autophagy in porcine parthenotes developing in vitro [5]. However, the role of autophagy in early porcine parthenotes is still poorly understood.A balance between the formation and degradation of cellular proteins is required for cell survival. In mammals, protein degradation is accelerated shortly after fertilization and is apparent by the early two-cell stage in mice [6] and the four-cell stage in pigs. Early embryogenesis may rely on maternal protein stores as nutrients. After fertilization, maternal proteins in oocytes are...

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supporting

confidence: 74%

Autophagy Influences Maternal mRNA Degradation and Apoptosis in Porcine Parthenotes Developing <i>In Vitro</i>

Shen

Lee

et al. 2012

Journal of Reproduction and Development

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“…On a molecular level, autophagic and apoptotic response machineries share some common pathways, for example, the PI3K/Akt signal pathway (28), MAPK / ERK1/2 signal pathway (29), and mitochondria pathway (30), which either link or polarize the cellular responses.…”

Section: Discussionmentioning

confidence: 99%

Silibinin Induced Autophagic and Apoptotic Cell Death in HT1080 Cells Through a Reactive Oxygen Species Pathway

Duan

Jin

et al. 2010

J Pharmacol Sci

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Abstract. Hepatoprotectant silibinin has anticancer and chemo-preventive effects. In this study, silibinin showed significant inhibitory effect on human fibroblast HT 1080 cell growth cultured in media containing 10% fetal bovine serum or in serum free media, and in the latter case, silibinin exerted a more significant effect. Silibinin induced autophagy at 12 h, confirmed by monodansylcadervarine (MDC) staining, up-regulation of Beclin 1 (initiation factor for autophagosome formation), and conversion of LC3 I to LC3 II (autophagosome marker). It also induced apoptosis at 24 h, proved by observation of apoptotic body and activation of caspase-3. 3-Methyladenine (3-MA) inhibited silibinin-induced autophagy and promoted cell survival, suggesting that autophagy enhanced silibinin-induced apoptosis in HT1080 cells. Silibinin generated reactive oxygen species (ROS) in HT1080 cells, and the ROS scavenger N -acetylcysteine (NAC) reversed the cytotoxicity of silibinin, resulting in cell survival by inhibition of autophagic and apoptotic pathways. Application of specific antioxidants demonstrated that H 2 O 2 was a major factor in silibinin-induced ROS since the H 2 O 2 scavenger catalase reduced both autophagy and cell death. O 2• − also contributed to silibinin-induced cell death.

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“…Because autophagy is involved in intracellular transport, not only linked to degradation, it was interesting to examine the involvement of such autophagic transport during NKG2D ligand surface expression. Autophagy is known to be induced by HDAC inhibitors (72,73), whereas there is conflicting data regarding whether selenium compounds activate or inhibit autophagy (74,75).…”

Section: The Nkg2d Ligand-regulating Effect Of Ch 3 Seh and An Hdac Imentioning

confidence: 99%

The Selenium Metabolite Methylselenol Regulates the Expression of Ligands That Trigger Immune Activation through the Lymphocyte Receptor NKG2D

Hagemann-Jensen

Uhlenbrock

Kehlet

et al. 2014

Journal of Biological Chemistry

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Background: Immune activation through a balanced cell surface expression of human NKG2D ligands is crucial for the elimination of diseased cells. Results: Methylselenol induces the expression of the NKG2D ligands MICA/B but specifically inhibits ULBP2 protein expression. Conclusion: Methylselenol regulates NKG2D ligand expression on transcriptional and posttranscriptional levels. Significance: Methylselenol is the first identified metabolite that diversely regulates NKG2D ligands, and, therefore, its implementation could improve NKG2D-based immune therapy.

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Autophagy inhibition through PI3K/Akt increases apoptosis by sodium selenite in NB4 cells

Cited by 73 publications

References 28 publications

Autophagy Influences Maternal mRNA Degradation and Apoptosis in Porcine Parthenotes Developing <i>In Vitro</i>

Autophagy Influences Maternal mRNA Degradation and Apoptosis in Porcine Parthenotes Developing <i>In Vitro</i>

Silibinin Induced Autophagic and Apoptotic Cell Death in HT1080 Cells Through a Reactive Oxygen Species Pathway

The Selenium Metabolite Methylselenol Regulates the Expression of Ligands That Trigger Immune Activation through the Lymphocyte Receptor NKG2D

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