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Control of the pericentrosomal H2O2 level by peroxiredoxin I is critical for mitotic progression.

Lim JM, Lee KS, Woo HA, Kang D, Rhee SG - J. Cell Biol. (2015)

Bottom Line: The intracellular concentration of H2O2 increases as the cell cycle progresses.Whereas the centrosome is shielded from H2O2 through its association with the H2O2-eliminating enzyme peroxiredoxin I (PrxI) during interphase, the centrosome-associated PrxI is selectively inactivated through phosphorylation by Cdk1 during early mitosis, thereby exposing the centrosome to H2O2 and facilitating inactivation of centrosome-bound phosphatases.Dephosphorylation of PrxI by okadaic acid-sensitive phosphatases during late mitosis again shields the centrosome from H2O2 and thereby allows the reactivation of Cdk1-opposing phosphatases at the organelle.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea.

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Sources of H2O2 produced during mitotic entry. (A–D) HeLa cells stably expressing histone H2B–GFP were synchronized at G1–S by thymidine treatment for 18 h, released into S phase in thymidine-free medium for 3 h, and then incubated in medium containing nocodazole and various concentrations of DPI (A), AACOCF3 (B), MAFP (C), or NDGA (D) for 10 h. The percentage of mitotic cells was then estimated on the basis of chromosome condensation and cell rounding. Data are means ± SD from three independent experiments. *, P < 0.05; **, P < 0.005 (Student’s t test).
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fig3: Sources of H2O2 produced during mitotic entry. (A–D) HeLa cells stably expressing histone H2B–GFP were synchronized at G1–S by thymidine treatment for 18 h, released into S phase in thymidine-free medium for 3 h, and then incubated in medium containing nocodazole and various concentrations of DPI (A), AACOCF3 (B), MAFP (C), or NDGA (D) for 10 h. The percentage of mitotic cells was then estimated on the basis of chromosome condensation and cell rounding. Data are means ± SD from three independent experiments. *, P < 0.05; **, P < 0.005 (Student’s t test).

Mentions: Reactive oxygen species including H2O2 increase gradually during cell cycle progression. There are multiple potential sources of H2O2 during mitosis, which include NADPH oxidase 4 (Yamaura et al., 2009) and arachidonic acid metabolism coupled to cPLA2 (cytosolic phospholipase A2; van Rossum et al., 2001; Cho et al., 2011). Indeed, we found that diphenyleneiodonium (DPI; NADPH oxidase inhibitor), AACOCF3 (cPLA2 inhibitor) and methyl arachidonyl fluorophosphonate (MAFP; cPLA2 inhibitor), and nordihydroguaiaretic acid (NDGA; lipoxygenase inhibitor) each attenuated mitotic entry in HeLa cells (Fig. 3, A–D). NADPH oxidase 4 and cPLA2 are localized to the membranes of ER, which accumulates around the centrosome before nuclear breakdown (Whitaker, 2006; Lassègue et al., 2012). It is therefore possible that sources of H2O2 are arranged specifically to channel H2O2 to the centrosome in mitotic cells.


Control of the pericentrosomal H2O2 level by peroxiredoxin I is critical for mitotic progression.

Lim JM, Lee KS, Woo HA, Kang D, Rhee SG - J. Cell Biol. (2015)

Sources of H2O2 produced during mitotic entry. (A–D) HeLa cells stably expressing histone H2B–GFP were synchronized at G1–S by thymidine treatment for 18 h, released into S phase in thymidine-free medium for 3 h, and then incubated in medium containing nocodazole and various concentrations of DPI (A), AACOCF3 (B), MAFP (C), or NDGA (D) for 10 h. The percentage of mitotic cells was then estimated on the basis of chromosome condensation and cell rounding. Data are means ± SD from three independent experiments. *, P < 0.05; **, P < 0.005 (Student’s t test).
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4493999&req=5

fig3: Sources of H2O2 produced during mitotic entry. (A–D) HeLa cells stably expressing histone H2B–GFP were synchronized at G1–S by thymidine treatment for 18 h, released into S phase in thymidine-free medium for 3 h, and then incubated in medium containing nocodazole and various concentrations of DPI (A), AACOCF3 (B), MAFP (C), or NDGA (D) for 10 h. The percentage of mitotic cells was then estimated on the basis of chromosome condensation and cell rounding. Data are means ± SD from three independent experiments. *, P < 0.05; **, P < 0.005 (Student’s t test).
Mentions: Reactive oxygen species including H2O2 increase gradually during cell cycle progression. There are multiple potential sources of H2O2 during mitosis, which include NADPH oxidase 4 (Yamaura et al., 2009) and arachidonic acid metabolism coupled to cPLA2 (cytosolic phospholipase A2; van Rossum et al., 2001; Cho et al., 2011). Indeed, we found that diphenyleneiodonium (DPI; NADPH oxidase inhibitor), AACOCF3 (cPLA2 inhibitor) and methyl arachidonyl fluorophosphonate (MAFP; cPLA2 inhibitor), and nordihydroguaiaretic acid (NDGA; lipoxygenase inhibitor) each attenuated mitotic entry in HeLa cells (Fig. 3, A–D). NADPH oxidase 4 and cPLA2 are localized to the membranes of ER, which accumulates around the centrosome before nuclear breakdown (Whitaker, 2006; Lassègue et al., 2012). It is therefore possible that sources of H2O2 are arranged specifically to channel H2O2 to the centrosome in mitotic cells.

Bottom Line: The intracellular concentration of H2O2 increases as the cell cycle progresses.Whereas the centrosome is shielded from H2O2 through its association with the H2O2-eliminating enzyme peroxiredoxin I (PrxI) during interphase, the centrosome-associated PrxI is selectively inactivated through phosphorylation by Cdk1 during early mitosis, thereby exposing the centrosome to H2O2 and facilitating inactivation of centrosome-bound phosphatases.Dephosphorylation of PrxI by okadaic acid-sensitive phosphatases during late mitosis again shields the centrosome from H2O2 and thereby allows the reactivation of Cdk1-opposing phosphatases at the organelle.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, South Korea.

Show MeSH
Related in: MedlinePlus