PMID- 32047576
OWN - NLM
STAT- MEDLINE
DCOM- 20200921
LR  - 20200921
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2020
DP  - 2020
TI  - Nitrative Stress-Related Autophagic Insufficiency Participates in 
      Hyperhomocysteinemia-Induced Renal Aging.
PG  - 4252047
LID - 10.1155/2020/4252047 [doi]
LID - 4252047
AB  - The kidneys are important organs that are susceptible to aging. 
      Hyperhomocysteinemia (HHcy) is a risk factor for nephropathy and is associated 
      with chronic nephritis, purpuric nephritis, and nephrotic syndrome. Numerous 
      studies have shown that elevated serum homocysteine levels can damage the 
      kidneys; however, the underlying mechanism of HHcy on kidney damage remains 
      unclear. In this study, we make use of a diet-induced HHcy rat model and in vitro 
      cell culture to explore the role of autophagy in HHcy-induced renal aging and 
      further explored the underlying mechanism. We demonstrated that HHcy led to the 
      development of renal aging. Promoted kidney aging and autophagic insufficiency 
      were involved in HHcy-induced renal aging. HHcy decreased the expression of 
      transcription factor EB (TFEB), the key transcription factor of autophagy-related 
      genes in renal tissue. Further experiments showed that nitrative stress levels 
      were increased in the kidney of HHcy rats. Interestingly, pretreatment with the 
      peroxynitrite (ONOO(-)) scavenger FeTMPyP not only reduced the Hcy-induced 
      nitrative stress in vitro but also partially attenuated the decrease in TFEB in 
      both protein and mRNA levels. Moreover, our results indicated that HHcy reduced 
      TFEB expression and inhibited TFEB-mediated autophagy activation by elevating 
      nitrative stress. In conclusion, this study showed an important role of 
      autophagic insufficiency in HHcy-induced renal aging, in which downregulation of 
      TFEB plays a major role. Furthermore, downexpression of TFEB was associated with 
      increased nitrative stress in HHcy. This study provides a novel insight into the 
      mechanism and therapeutic strategy for renal aging.
CI  - Copyright (c) 2020 Shangyue Zhang et al.
FAU - Zhang, Shangyue
AU  - Zhang S
AUID- ORCID: 0000-0002-6741-3577
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing, China.
FAU - Zhang, Yuerong
AU  - Zhang Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing, China.
FAU - Zhang, Xinyu
AU  - Zhang X
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing, China.
FAU - Luo, Chenghua
AU  - Luo C
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing, China.
FAU - Cao, Yan
AU  - Cao Y
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing, China.
FAU - Ji, Dengyu
AU  - Ji D
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing, China.
FAU - Yan, Wenjing
AU  - Yan W
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing, China.
FAU - Xue, Ke
AU  - Xue K
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing, China.
FAU - Chai, Jiayin
AU  - Chai J
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing, China.
FAU - Dai, Hongyan
AU  - Dai H
AUID- ORCID: 0000-0001-6088-9532
AD  - Department of Cardiology, Qingdao Municipal Hospital, Qingdao, Shandong, China.
FAU - Wang, Wen
AU  - Wang W
AUID- ORCID: 0000-0003-4120-0773
AD  - Department of Physiology and Pathophysiology, School of Basic Medical Sciences, 
      Capital Medical University, Beijing, China.
AD  - Beijing Key Laboratory of Metabolic Disorders Related Cardiovascular Diseases, 
      Capital Medical University, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20200125
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (5,10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato-iron(III))
RN  - 0 (Metalloporphyrins)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 14691-52-2 (Peroxynitrous Acid)
SB  - IM
MH  - Aging/*physiology
MH  - Animals
MH  - Autophagy
MH  - Cells, Cultured
MH  - Homocysteine/*metabolism
MH  - Humans
MH  - Hyperhomocysteinemia/*metabolism
MH  - Kidney/*physiology
MH  - Kidney Diseases/*metabolism
MH  - Male
MH  - Metalloporphyrins
MH  - Peroxynitrous Acid/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC7007752
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2020/02/13 06:00
MHDA- 2020/09/22 06:00
PMCR- 2020/01/25
CRDT- 2020/02/13 06:00
PHST- 2019/10/10 00:00 [received]
PHST- 2019/12/25 00:00 [revised]
PHST- 2020/01/10 00:00 [accepted]
PHST- 2020/02/13 06:00 [entrez]
PHST- 2020/02/13 06:00 [pubmed]
PHST- 2020/09/22 06:00 [medline]
PHST- 2020/01/25 00:00 [pmc-release]
AID - 10.1155/2020/4252047 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2020 Jan 25;2020:4252047. doi: 10.1155/2020/4252047. 
      eCollection 2020.