期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 18, 期 10, 页码 -出版社
MDPI
DOI: 10.3390/ijms18102081
关键词
ischemia-reperfusion injury (IRI); fat-1 transgenic mice; AMP-activated protein kinase (AMPK); autophagy
资金
- National Research Foundation of Korea (NRF)
- Korea government (MSIP) at Chungnam National University [2016R1C1B1015811]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [NRF-2010-0024594]
- Chungnam National University Hospital Research Fund
- National Research Foundation of Korea [2016R1C1B1015811] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Regulated autophagy is involved in the repair of renal ischemia-reperfusion injury (IRI). Fat-1 transgenic mice produce omega 3-Polyunsaturated fatty acids (omega 3-PUFAs) from 6-Polyunsaturated fatty acids (omega 6-PUFAs) without a dietary omega 3-PUFAs supplement, leading to a high accumulation of omega-3 in various tissues. omega 3-PUFAs show protective effects against various renal injuries and it has recently been reported that omega 3-PUFAs regulate autophagy. We assessed whether omega 3-PUFAs attenuated IR-induced acute kidney injury (AKI) and evaluated its associated mechanisms. C57Bl/6 background fat-1 mice and wild-type mice (wt) were divided into four groups: wt sham (n = 10), fat-1 sham (n = 10), wt IRI (reperfusion 35 min after clamping both the renal artery and vein; n = 15), and fat-1 IRI (n = 15). Kidneys and blood were harvested 24 h after IRI and renal histological and molecular data were collected. The kidneys of fat-1 mice showed better renal cell survival, renal function, and pathological damage than those of wt mice after IRI. In addition, fat-1 mice showed less oxidative stress and autophagy impairment; greater amounts of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II, Beclin-1, and Atg7; lower amounts of p62; and, higher levels of renal cathepsin D and ATP6E than wt kidneys. They also showed more adenosine monophosphate-activated protein kinase (AMPK) activation, which resulted in the inhibition of phosphorylation of the mammalian target of rapamycin (mTOR). Collectively, omega 3-PUFAs in fat-1 mice contributed to AMPK mediated autophagy activation, leading to a renoprotective response.
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