PMID- 36277207
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221025
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 13
DP  - 2022
TI  - Hyperhomocysteinemia exacerbates acute kidney injury via increased mitochondrial 
      damage.
PG  - 967104
LID - 10.3389/fphys.2022.967104 [doi]
LID - 967104
AB  - Acute kidney injury (AKI) is a complex and common set of multifactorial clinical 
      syndromes, and associated with increased in-hospital mortality. There is 
      increasing evidence that Hyperhomocysteinemia (HHcy) is highly associated with 
      the development of a variety of kidney diseases, including AKI. However, the 
      pathogenesis of HHcy in AKI remains unclear. In this study, we investigated the 
      effect and mechanism of HHcy on cisplatin-induced AKI in mice and NRK-52E cells 
      cultured with HHcy. We confirmed that mice with HHcy had higher serum levels of 
      creatinine and more severe renal tubule injury after cisplatin injection. We 
      found that HHcy aggravated renal mitochondrial damage, mainly manifested as 
      decreased ATP beta, significantly increased cytoplasmic Cyt C expression and the 
      ADP/ATP ratio, and a significantly decreased mitochondrial DNA (mtDNA) copy 
      number. In addition, we found that HHcy accelerated cisplatin-induced renal DNA 
      damage; culturing NRK-52E cells with homocysteine (Hcy) could significantly 
      increase apoptosis and mitochondrial damage. Interestingly, we found that Mdivi-1 
      reduced Hcy-induced mitochondrial damage, thereby reducing the level of 
      apoptosis. In conclusion, these results suggest that HHcy might aggravate the 
      development of AKI by increasing mitochondrial damage and that reducing Hcy 
      levels or inhibiting mitochondrial damage may be a potential therapeutic strategy 
      to delay the development of AKI.
CI  - Copyright (c) 2022 Zhang, Dong, Da, Yuan, Zha and Long.
FAU - Zhang, Mei
AU  - Zhang M
AD  - Department of Nephrology, Guizhou Provincial Institute of Nephritic & Urinary 
      Disease, Guizhou Provincial People's Hospital, Guiyang, China.
FAU - Dong, Rong
AU  - Dong R
AD  - Department of Nephrology, Guizhou Provincial Institute of Nephritic & Urinary 
      Disease, Guizhou Provincial People's Hospital, Guiyang, China.
FAU - Da, Jingjing
AU  - Da J
AD  - Department of Nephrology, Guizhou Provincial Institute of Nephritic & Urinary 
      Disease, Guizhou Provincial People's Hospital, Guiyang, China.
AD  - Department of Biomedicine, Guizhou University School of Medicine, Guizhou 
      University, Guiyang, China.
FAU - Yuan, Jing
AU  - Yuan J
AD  - Department of Nephrology, Guizhou Provincial Institute of Nephritic & Urinary 
      Disease, Guizhou Provincial People's Hospital, Guiyang, China.
AD  - Department of Biomedicine, Guizhou University School of Medicine, Guizhou 
      University, Guiyang, China.
FAU - Zha, Yan
AU  - Zha Y
AD  - Department of Nephrology, Guizhou Provincial Institute of Nephritic & Urinary 
      Disease, Guizhou Provincial People's Hospital, Guiyang, China.
AD  - Department of Biomedicine, Guizhou University School of Medicine, Guizhou 
      University, Guiyang, China.
FAU - Long, Yanjun
AU  - Long Y
AD  - Department of Nephrology, Guizhou Provincial Institute of Nephritic & Urinary 
      Disease, Guizhou Provincial People's Hospital, Guiyang, China.
AD  - Department of Biomedicine, Guizhou University School of Medicine, Guizhou 
      University, Guiyang, China.
AD  - Department of Nephrology, People's Hospital of Zhenfeng County, Qianxinan, 
      Guizhou, China.
LA  - eng
PT  - Journal Article
DEP - 20221005
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC9581205
OTO - NOTNLM
OT  - DNA damage
OT  - Hyperhomocysteinemia
OT  - acute kidney injury
OT  - apoptosis
OT  - mitochondrial damage
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/10/25 06:00
MHDA- 2022/10/25 06:01
PMCR- 2022/10/05
CRDT- 2022/10/24 04:28
PHST- 2022/06/12 00:00 [received]
PHST- 2022/09/20 00:00 [accepted]
PHST- 2022/10/24 04:28 [entrez]
PHST- 2022/10/25 06:00 [pubmed]
PHST- 2022/10/25 06:01 [medline]
PHST- 2022/10/05 00:00 [pmc-release]
AID - 967104 [pii]
AID - 10.3389/fphys.2022.967104 [doi]
PST - epublish
SO  - Front Physiol. 2022 Oct 5;13:967104. doi: 10.3389/fphys.2022.967104. eCollection 
      2022.