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Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation.

Hytti M, Piippo N, Korhonen E, Honkakoski P, Kaarniranta K, Kauppinen A - Sci Rep (2015)

Bottom Line: Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation.The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1.The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio, Finland.

ABSTRACT
Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

No MeSH data available.


Related in: MedlinePlus

The growth of ARPE-19 cells in serum-containing (SC) or serum-free medium (SF).Cells in serum-free medium were slower to spread out on the surface and start the growth phase but reached confluency after 72 h. White arrows indicate spindle-like protrusions from growing ARPE-19 cells.
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f1: The growth of ARPE-19 cells in serum-containing (SC) or serum-free medium (SF).Cells in serum-free medium were slower to spread out on the surface and start the growth phase but reached confluency after 72 h. White arrows indicate spindle-like protrusions from growing ARPE-19 cells.

Mentions: In order to induce increased stress, ARPE-19 cells were placed directly after splitting into serum-free medium for all experiments and incubated for up to 72 h in a humidified cell incubator at +37 °C. During the incubation, we monitored the cell growth rate in serum-free medium and compared it to the growth rate of cells maintained under the same conditions in serum-containing medium. Pictures taken 6, 12, 24, 48, and 72 h after plating highlight that it took longer for ARPE-19 cells to adhere to the plate and spread out when cultivated in the serum-free medium when compared to those cultured in the serum-containing medium (Fig. 1). The same phenomenon can also be observed in a time-lapse video of cell attachment (Supplementary material). Those cells cultured in serum-containing medium attached to the surface and spread quicker (Suppl. Video 1) when compared to cells cultured in serum-free medium (Suppl. Video 2). Once they had spread out, however, cells in the serum-free medium grew at a rate similar to that observed for cells cultured in the serum-containing medium (Suppl. Fig. 2). Cells cultured in either medium showed a transient phenotype with spindle-like appearances, which occurred earlier in the cells cultured in serum-containing medium (Fig. 1, white arrows). Irrespective of the presence or absence of serum in the culture medium, ARPE-19 cells reached full confluency and expressed a normal phenotype once confluent.


Fisetin and luteolin protect human retinal pigment epithelial cells from oxidative stress-induced cell death and regulate inflammation.

Hytti M, Piippo N, Korhonen E, Honkakoski P, Kaarniranta K, Kauppinen A - Sci Rep (2015)

The growth of ARPE-19 cells in serum-containing (SC) or serum-free medium (SF).Cells in serum-free medium were slower to spread out on the surface and start the growth phase but reached confluency after 72 h. White arrows indicate spindle-like protrusions from growing ARPE-19 cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664957&req=5

f1: The growth of ARPE-19 cells in serum-containing (SC) or serum-free medium (SF).Cells in serum-free medium were slower to spread out on the surface and start the growth phase but reached confluency after 72 h. White arrows indicate spindle-like protrusions from growing ARPE-19 cells.
Mentions: In order to induce increased stress, ARPE-19 cells were placed directly after splitting into serum-free medium for all experiments and incubated for up to 72 h in a humidified cell incubator at +37 °C. During the incubation, we monitored the cell growth rate in serum-free medium and compared it to the growth rate of cells maintained under the same conditions in serum-containing medium. Pictures taken 6, 12, 24, 48, and 72 h after plating highlight that it took longer for ARPE-19 cells to adhere to the plate and spread out when cultivated in the serum-free medium when compared to those cultured in the serum-containing medium (Fig. 1). The same phenomenon can also be observed in a time-lapse video of cell attachment (Supplementary material). Those cells cultured in serum-containing medium attached to the surface and spread quicker (Suppl. Video 1) when compared to cells cultured in serum-free medium (Suppl. Video 2). Once they had spread out, however, cells in the serum-free medium grew at a rate similar to that observed for cells cultured in the serum-containing medium (Suppl. Fig. 2). Cells cultured in either medium showed a transient phenotype with spindle-like appearances, which occurred earlier in the cells cultured in serum-containing medium (Fig. 1, white arrows). Irrespective of the presence or absence of serum in the culture medium, ARPE-19 cells reached full confluency and expressed a normal phenotype once confluent.

Bottom Line: Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation.The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1.The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O.B. 1627, FI-70211, Kuopio, Finland.

ABSTRACT
Degeneration of retinal pigment epithelial (RPE) cells is a clinical hallmark of age-related macular degeneration (AMD), the leading cause of blindness among aged people in the Western world. Both inflammation and oxidative stress are known to play vital roles in the development of this disease. Here, we assess the ability of fisetin and luteolin, to protect ARPE-19 cells from oxidative stress-induced cell death and to decrease intracellular inflammation. We also compare the growth and reactivity of human ARPE-19 cells in serum-free and serum-containing conditions. The absence of serum in the culture medium did not prevent ARPE-19 cells from reaching full confluency but caused an increased sensitivity to oxidative stress-induced cell death. Both fisetin and luteolin protected ARPE-19 cells from oxidative stress-induced cell death. They also significantly decreased the release of pro-inflammatory cytokines into the culture medium. The decrease in inflammation was associated with reduced activation of MAPKs and CREB, but was not linked to NF- κB or SIRT1. The ability of fisetin and luteolin to protect and repair stressed RPE cells even after the oxidative insult make them attractive in the search for treatments for AMD.

No MeSH data available.


Related in: MedlinePlus