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Interrelationship between activation of matrix metalloproteinases and mitochondrial dysfunction in the development of diabetic retinopathy.

Abstract：

:Mitochondria dysfunction plays a significant role in the apoptosis of retinal cells. Diabetes activates retinal matrix metalloproteinases (MMP-9 and MMP-2), damages retinal mitochondria and activates the apoptotic machinery. This study is to investigate the temporal relationship between the activation of retinal MMPs and mitochondria damage in the development of diabetic retinopathy. Time course of activation of cytosolic MMP-9 and MMP-2 was investigated in the retinal endothelial cells incubated in high glucose for 6-96 h, and correlated with their mitochondrial accumulation and mitochondrial damage. This was confirmed in the retina from rats diabetic for 15 days to ~12 months (streptozotocin-induced). The results show that the activation of cytosolic MMP-9 and MMP-2 is an early event, which is followed by their accumulation in the mitochondria. Increased mitochondrial MMPs dysfunction them and begin to damage their DNA, which initiates a vicious cycle of reactive oxygen species. Thus, modulation of these gelatinase MMPs by pharmacological agents during the early stages of diabetes could provide a strategy to inhibit the development of diabetic retinopathy.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Santos JM,Tewari S,Lin JY,Kowluru RA

doi

10.1016/j.bbrc.2013.07.066

subject

Has Abstract

pub_date

2013-09-06 00:00:00

pages

760-4

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(13)01226-6

journal_volume

438

pub_type

杂志文章

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