Phloretin inhibits glucose transport and reduces inflammation in human retinal pigment epithelial cells

被引:18
|
作者
Hytti, Maria [1 ]
Ruuth, Johanna [1 ,2 ]
Kanerva, Iiris [1 ]
Bhattarai, Niina [1 ]
Pedersen, Maria L. [3 ]
Nielsen, Carsten U. [3 ]
Kauppinen, Anu [1 ]
机构
[1] Univ Eastern Finland, Dept Hlth Sci, Sch Pharm, Yliopistonranta 1 C, Kuopio 70210, Finland
[2] Univ Eastern Finland, Dept Hlth Sci, Sch Med, Yliopistonranta 1 C, Kuopio 70210, Finland
[3] Univ Southern Denmark, Dept Phys Chem & Pharm, Campusvej 55, DK-5230 Odense, Denmark
基金
芬兰科学院;
关键词
Retinal degeneration; Inflammation; Phloretin; Glucose transport; Nuclear factor erythroid 2-related factor 2 (Nrf2); NF-KAPPA-B; BIOACTIVE COMPOUNDS; ICAM-1; EXPRESSION; APPLE; ACTIVATION; GENE; APOPTOSIS; PATHWAYS; STRESS; GINGER;
D O I
10.1007/s11010-022-04504-2
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
During age-related macular degeneration (AMD), chronic inflammatory processes, possibly fueled by high glucose levels, cause a breakdown of the retinal pigment epithelium (RPE), leading to vision loss. Phloretin, a natural dihydroxychalcone found in apples, targets several anti-inflammatory signaling pathways and effectively inhibits transporter-mediated glucose uptake. It could potentially prevent inflammation and cell death of RPE cells through either direct regulation of inflammatory signaling pathways or through amelioration of high glucose levels. To test this hypothesis, ARPE-19 cells were incubated with or without phloretin for 1 h before exposure to lipopolysaccharide (LPS). Cell viability and the release of pro-inflammatory cytokines interleukin 6 (IL-6), IL-8 and vascular endothelial growth factor (VEGF) were measured. Glucose uptake was studied using isotope uptake studies. The nuclear levels of nuclear factor erythroid 2-related factor 2 (Nrf2) were determined alongside the phosphorylation levels of mitogen-activated protein kinases. Phloretin pretreatment reduced the LPS-induced release of IL-6 and IL-8 as well as VEGF. Phloretin increased intracellular levels of reactive oxygen species and nuclear translocation of Nrf2. It also inhibited glucose uptake into ARPE-19 cells and the phosphorylation of Jun-activated kinase (JNK). Subsequent studies revealed that Nrf2, but not the inhibition of glucose uptake or JNK phosphorylation, was the main pathway of phloretin's anti-inflammatory activities. Phloretin was robustly anti-inflammatory in RPE cells and reduced IL-8 secretion via activation of Nrf2 but the evaluation of its potential in the treatment or prevention of AMD requires further studies.
引用
收藏
页码:215 / 227
页数:13
相关论文
共 50 条
  • [41] Plasticity of adult human retinal pigment epithelial cells
    Kuznetsova, Alla V.
    Aleksandrova, Maria A.
    Kurinov, Alexander M.
    Chentsova, Ekaterina V.
    Makarov, Pavel V.
    INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE, 2016, 9 (11): : 20892 - 20906
  • [42] ULTRASTRUCTURE OF RETINAL PIGMENT EPITHELIAL CELLS IN HUMAN FOETUS
    BREATHNA.AS
    WYLLIE, LMA
    JOURNAL OF ANATOMY, 1966, 100 : 700 - &
  • [43] Photocytotoxicity of lipofuscin in human retinal pigment epithelial cells
    Davies, S
    Elliott, MH
    Floor, E
    Truscot, TG
    Zareba, M
    Sarna, T
    Shamsi, FA
    Boulton, ME
    FREE RADICAL BIOLOGY AND MEDICINE, 2001, 31 (02) : 256 - 265
  • [44] Adrenomedullin in cultured human retinal pigment epithelial cells
    Udono, T
    Takahashi, K
    Nakayama, M
    Murakami, O
    Durlu, YK
    Tamai, M
    Shibahara, S
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2000, 41 (07) : 1962 - 1970
  • [45] Luteolin decreases mitochondrial damage-associated inflammation in human retinal pigment epithelial cells
    Hytti, Maria
    Korhonen, Eveliina
    Piippo, Niina
    Kaarniranta, Kai
    Kauppinen, Anu
    INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 2017, 58 (08)
  • [46] Magnolol inhibits high glucose or AGEs-induced VEGF and TGF-beta expression in human retinal pigment epithelial cells
    Kim, Young Sook
    Jung, Dong Ho
    Kim, Nan Hee
    Kim, Jin Sook
    DIABETES, 2006, 55 : A468 - A468
  • [47] Nintedanib inhibits normal human vitreous-induced epithelial-mesenchymal transition in human retinal pigment epithelial cells
    Yin, Yiwei
    Liu, Shikun
    Liu, Hanhan
    Wu, Wenyi
    BIOMEDICINE & PHARMACOTHERAPY, 2023, 166
  • [48] Concanavalin A Inhibits Melanosome Aggregation in Isolated Retinal Pigment Epithelial Cells
    Gannon, P.
    King-Smith, C.
    MOLECULAR BIOLOGY OF THE CELL, 2006, 17
  • [49] Ascorbic acid reversibly inhibits proliferation of retinal pigment epithelial cells
    Heckelen, A
    Hermel, M
    Kondring, B
    Schrage, NF
    ACTA OPHTHALMOLOGICA SCANDINAVICA, 2004, 82 (05): : 564 - 568
  • [50] Glucose specific regulation of aldose reductase in human retinal pigment epithelial (RPE) cells in vitro
    Henry, DN
    Hootman, SR
    Rood, SE
    Busik, JV
    DIABETES, 1999, 48 : A157 - A157