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Biochem Biophys Res Commun. 2018 Sep 10;503(3):1307-1314. doi: 10.1016/j.bbrc.2018.07.041. Epub 2018 Jul 11.

Alpha-lipoic acid reduces retinal cell death in diabetic mice.

Author information

1
Department of Anatomy and Convergence Medical Science, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea.
2
Medvill Co., Ltd, 1606 Daeryung Post Tower 5th, 68 Digitalro 9gil, Guemcheon-gu, Seoul, 08512, Republic of Korea.
3
Department of Anatomy and Convergence Medical Science, Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, Gyeongnam, Republic of Korea. Electronic address: choiws@gnu.kr.

Abstract

Oxidative stress plays an important role in the development of diabetic retinopathy. Here, we examined whether α-lipoic acid (α-LA), a natural antioxidant, attenuated retinal injury in diabetic mice. The α-LA was orally administered to control mice or mice with streptozotocin-induced diabetes. We found that α-LA reduced oxidative stress, decreased and increased retinal 4-hydroxy-2-nonenal and glutathione peroxidase, respectively, and inhibited retinal cell death. Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose. Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells. Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells. Consistently, α-LA lowered the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3 in diabetic retinas. Our results indicated that α-LA reduced retinal cell death partly through AMPK activation or OGT inhibition in diabetic mice.

KEYWORDS:

AMPK; OGT; PPARδ; SIRT3; TXNIP

PMID:
30017190
DOI:
10.1016/j.bbrc.2018.07.041
[Indexed for MEDLINE]

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