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Combined activation of the energy and cellular-defense pathways may explain the potent anti-senescence activity of methylene blue.

Atamna H, Atamna W, Al-Eyd G, Shanower G, Dhahbi JM - Redox Biol (2015)

Bottom Line: Methylene blue (MB) delays cellular senescence, induces complex-IV, and activates Keap1/Nrf2; however, the molecular link of these effects to MB is unclear.A previous research suggested that the pattern of AMPK activation (i.e., chronic or transient) determines the AMPK effect on cell senescence.Since MB lacked an effect on cell cycle, an MB-dependent change to cell cycle is unlikely to contribute to the anti-senescence activity.

View Article: PubMed Central - PubMed

Affiliation: College of Medicine, California University of Science & Medicine, Colton, CA 92324, USA; Department of Basic Sciences, The Commonwealth Medical College (TCMC), Scranton, PA 18509, USA. Electronic address: atamnah@calmedu.org.

No MeSH data available.


Related in: MedlinePlus

Comparing the anti-senescence activity of AICAR to MB. IMR90 cells were maintained with MB, AICAR, or control until they senesce. The senescence of IMR90 cells was measured by continuously maintaining the cells in culture as described in Materials and Methods. The control cells gained 66 PDLs and senesced at week 11 (closed squares), 100 nM MB-treated cells gained 84 PDLs and senesced at week 17 (open squares), the 50 µM AICAR-treated cells gained 65.4 PDLs and senesced at week 11 (closed circles), and 100 µM AICAR-treated cells gained 68.1 PDLs and senesced at week 12 (open circles). Each time point represents the average of the PDLs that were calculated from three independent experiments. The data shown is the Mean±sem. One-way ANOVA, Dunnett's multiple comparisons test. *P<0.05, ***P<0.001.
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f0050: Comparing the anti-senescence activity of AICAR to MB. IMR90 cells were maintained with MB, AICAR, or control until they senesce. The senescence of IMR90 cells was measured by continuously maintaining the cells in culture as described in Materials and Methods. The control cells gained 66 PDLs and senesced at week 11 (closed squares), 100 nM MB-treated cells gained 84 PDLs and senesced at week 17 (open squares), the 50 µM AICAR-treated cells gained 65.4 PDLs and senesced at week 11 (closed circles), and 100 µM AICAR-treated cells gained 68.1 PDLs and senesced at week 12 (open circles). Each time point represents the average of the PDLs that were calculated from three independent experiments. The data shown is the Mean±sem. One-way ANOVA, Dunnett's multiple comparisons test. *P<0.05, ***P<0.001.

Mentions: The anti-senescence activity of AICAR (a chronic activator of AMPK) was compared to that of MB. The nontoxic concentration of AICAR was determined based on a pilot experiment, which demonstrated 50 µM and 100 µM to be optimal for testing the effect of AICAR on cell senescence (Data not shown). At 50 µM, AICAR has no effect on cell senescence (Fig. 10). At 100 µM, on the other hand, AICAR has positive but small effect on cell senescence (Fig. 10). The control cultures senesced at PDL 66 (Fig. 10). The gain in PDL by 100 µM AICAR was 2.1 PDLs (P<0.05) as compared to 18 PDLs (P<0.001) gained by 100 nM MB, which make the final PDL at senescence to be 68.1 and 84 PDLs, respectively (Fig. 10). Thus, MB causes large gain in total PDL. Furthermore, AICAR prolonged the interval until the cell culture reached senescence by one week beyond the control culture while MB prolonged the interval until the cell culture reached senescence by 6 weeks beyond the control culture (Fig. 10). It is important to emphasize that the anti-senescence activity of MB requires a concentration that is 1000 times less than AICAR (100 nM MB vs. 100 µM AICAR).


Combined activation of the energy and cellular-defense pathways may explain the potent anti-senescence activity of methylene blue.

Atamna H, Atamna W, Al-Eyd G, Shanower G, Dhahbi JM - Redox Biol (2015)

Comparing the anti-senescence activity of AICAR to MB. IMR90 cells were maintained with MB, AICAR, or control until they senesce. The senescence of IMR90 cells was measured by continuously maintaining the cells in culture as described in Materials and Methods. The control cells gained 66 PDLs and senesced at week 11 (closed squares), 100 nM MB-treated cells gained 84 PDLs and senesced at week 17 (open squares), the 50 µM AICAR-treated cells gained 65.4 PDLs and senesced at week 11 (closed circles), and 100 µM AICAR-treated cells gained 68.1 PDLs and senesced at week 12 (open circles). Each time point represents the average of the PDLs that were calculated from three independent experiments. The data shown is the Mean±sem. One-way ANOVA, Dunnett's multiple comparisons test. *P<0.05, ***P<0.001.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588422&req=5

f0050: Comparing the anti-senescence activity of AICAR to MB. IMR90 cells were maintained with MB, AICAR, or control until they senesce. The senescence of IMR90 cells was measured by continuously maintaining the cells in culture as described in Materials and Methods. The control cells gained 66 PDLs and senesced at week 11 (closed squares), 100 nM MB-treated cells gained 84 PDLs and senesced at week 17 (open squares), the 50 µM AICAR-treated cells gained 65.4 PDLs and senesced at week 11 (closed circles), and 100 µM AICAR-treated cells gained 68.1 PDLs and senesced at week 12 (open circles). Each time point represents the average of the PDLs that were calculated from three independent experiments. The data shown is the Mean±sem. One-way ANOVA, Dunnett's multiple comparisons test. *P<0.05, ***P<0.001.
Mentions: The anti-senescence activity of AICAR (a chronic activator of AMPK) was compared to that of MB. The nontoxic concentration of AICAR was determined based on a pilot experiment, which demonstrated 50 µM and 100 µM to be optimal for testing the effect of AICAR on cell senescence (Data not shown). At 50 µM, AICAR has no effect on cell senescence (Fig. 10). At 100 µM, on the other hand, AICAR has positive but small effect on cell senescence (Fig. 10). The control cultures senesced at PDL 66 (Fig. 10). The gain in PDL by 100 µM AICAR was 2.1 PDLs (P<0.05) as compared to 18 PDLs (P<0.001) gained by 100 nM MB, which make the final PDL at senescence to be 68.1 and 84 PDLs, respectively (Fig. 10). Thus, MB causes large gain in total PDL. Furthermore, AICAR prolonged the interval until the cell culture reached senescence by one week beyond the control culture while MB prolonged the interval until the cell culture reached senescence by 6 weeks beyond the control culture (Fig. 10). It is important to emphasize that the anti-senescence activity of MB requires a concentration that is 1000 times less than AICAR (100 nM MB vs. 100 µM AICAR).

Bottom Line: Methylene blue (MB) delays cellular senescence, induces complex-IV, and activates Keap1/Nrf2; however, the molecular link of these effects to MB is unclear.A previous research suggested that the pattern of AMPK activation (i.e., chronic or transient) determines the AMPK effect on cell senescence.Since MB lacked an effect on cell cycle, an MB-dependent change to cell cycle is unlikely to contribute to the anti-senescence activity.

View Article: PubMed Central - PubMed

Affiliation: College of Medicine, California University of Science & Medicine, Colton, CA 92324, USA; Department of Basic Sciences, The Commonwealth Medical College (TCMC), Scranton, PA 18509, USA. Electronic address: atamnah@calmedu.org.

No MeSH data available.


Related in: MedlinePlus