Citation
Mitter, Sayak K., et al. "Dysregulated Autophagy in the RPE Is Associated With Increased Susceptibility to Oxidative Stress and AMD." Autophagy, vol. 10, no. 11, 2014, pp. 1989-2005.
Mitter SK, Song C, Qi X, et al. Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD. Autophagy. 2014;10(11):1989-2005.
Mitter, S. K., Song, C., Qi, X., Mao, H., Rao, H., Akin, D., Lewin, A., Grant, M., Dunn, W., Ding, J., Bowes Rickman, C., & Boulton, M. (2014). Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD. Autophagy, 10(11), 1989-2005. https://doi.org/10.4161/auto.36184
Mitter SK, et al. Dysregulated Autophagy in the RPE Is Associated With Increased Susceptibility to Oxidative Stress and AMD. Autophagy. 2014;10(11):1989-2005. PubMed PMID: 25484094.
TY - JOUR
T1 - Dysregulated autophagy in the RPE is associated with increased susceptibility to oxidative stress and AMD.
AU - Mitter,Sayak K,
AU - Song,Chunjuan,
AU - Qi,Xiaoping,
AU - Mao,Haoyu,
AU - Rao,Haripriya,
AU - Akin,Debra,
AU - Lewin,Alfred,
AU - Grant,Maria,
AU - Dunn,William,Jr
AU - Ding,Jindong,
AU - Bowes Rickman,Catherine,
AU - Boulton,Michael,
PY - 2014/12/9/entrez
PY - 2014/12/9/pubmed
PY - 2015/9/15/medline
KW - 3-MA, 3-methyladenine
KW - ACTB, β-actin
KW - AMD, age-related macular degeneration
KW - APOE4, apolipoprotein E4
KW - FACS, fluorescence-activated cell sorting
KW - FBS, fetal bovine serum
KW - GFP, green fluorescent protein
KW - GSH, glutathione, reduced
KW - GSSG, glutathione, oxidized
KW - H2O2, hydrogen peroxide
KW - HFC, high fat, cholesterol-enriched diet
KW - LC3, microtubule-associated protein 1 light chain 3
KW - MMP, mitochondrial membrane potential
KW - MTT, 3-(4 5-dimethylthiazol-3-yl)-2, 5-diphenyl tetrazolium bromide
KW - ND, normal (rodent) diet
KW - POS, photoreceptor outer segments
KW - ROS, reactive oxygen species
KW - RPE
KW - RPE, retinal pigmented epithelium
KW - SOD2/MnSOD, superoxide dismutase 2, mitochondrial
KW - UPS, ubiquitin-proteasome system
KW - age-related macular degeneration
KW - aging
KW - autophagy
KW - oxidative stress
SP - 1989
EP - 2005
JF - Autophagy
JO - Autophagy
VL - 10
IS - 11
N2 - Autophagic dysregulation has been suggested in a broad range of neurodegenerative diseases including age-related macular degeneration (AMD). To test whether the autophagy pathway plays a critical role to protect retinal pigmented epithelial (RPE) cells against oxidative stress, we exposed ARPE-19 and primary cultured human RPE cells to both acute (3 and 24 h) and chronic (14 d) oxidative stress and monitored autophagy by western blot, PCR, and autophagosome counts in the presence or absence of autophagy modulators. Acute oxidative stress led to a marked increase in autophagy in the RPE, whereas autophagy was reduced under chronic oxidative stress. Upregulation of autophagy by rapamycin decreased oxidative stress-induced generation of reactive oxygen species (ROS), whereas inhibition of autophagy by 3-methyladenine (3-MA) or by knockdown of ATG7 or BECN1 increased ROS generation, exacerbated oxidative stress-induced reduction of mitochondrial activity, reduced cell viability, and increased lipofuscin. Examination of control human donor specimens and mice demonstrated an age-related increase in autophagosome numbers and expression of autophagy proteins. However, autophagy proteins, autophagosomes, and autophagy flux were significantly reduced in tissue from human donor AMD eyes and 2 animal models of AMD. In conclusion, our data confirm that autophagy plays an important role in protection of the RPE against oxidative stress and lipofuscin accumulation and that impairment of autophagy is likely to exacerbate oxidative stress and contribute to the pathogenesis of AMD.
SN - 1554-8635
UR - https://www.unboundmedicine.com/medline/citation/25484094/Dysregulated_autophagy_in_the_RPE_is_associated_with_increased_susceptibility_to_oxidative_stress_and_AMD_
L2 - https://www.tandfonline.com/doi/full/10.4161/auto.36184
DB - PRIME
DP - Unbound Medicine
ER -