PMID- 37186061
OWN - NLM
STAT- MEDLINE
DCOM- 20230811
LR  - 20230811
IS  - 1099-0461 (Electronic)
IS  - 1095-6670 (Linking)
VI  - 37
IP  - 8
DP  - 2023 Aug
TI  - Ox-LDL aggravates contrast-induced injury of renal tubular epithelial cells.
PG  - e23379
LID - 10.1002/jbt.23379 [doi]
AB  - Hypercholesterolemia can aggravate contrast-induced acute kidney injury, and the 
      exacerbation of renal tubular epithelial cell (RTEC) injury is a major cause. 
      However, the exact mechanisms remain obscure. Mitophagy, a type of autophagy, 
      selectively eliminates damaged mitochondria and reduces mitochondrial oxidative 
      stress, which is strongly implicated in cell homeostasis and acute kidney injury. 
      Oxidized low-density lipoprotein (Ox-LDL) is accumulated in hypercholesterolemia 
      and has a cytotoxic effect. This study aimed to determine whether and how ox-LDL 
      exacerbates contrast-induced injury in RTECs and to further explore whether 
      PINK1/Parkin-dependent mitophagy is involved in this process. Iohexol and ox-LDL 
      were used alone or in combination to treat HK-2 cells. Rapamycin pretreatment was 
      utilized to enhance mitophagy. Cell viability, apoptosis, mitochondrial membrane 
      potential (MMP) and mitochondrial reactive oxygen species (mtROS) were detected 
      by cell counting kit-8, TUNEL staining, JC-1 kit and MitoSOX fluorescence, 
      respectively. The expression of mitophagy-related proteins (including PINK1, 
      Parkin, and so on) and cleaved caspase-3 was confirmed by western blot. 
      Colocalization of MitoTracker-labeled mitochondria and LysoTracker-labeled 
      lysosomes was observed by fluorescence microscopy to evaluate mitophagy. The 
      results of our study showed that ox-LDL aggravated MMP decline, mtROS release and 
      apoptosis in iohexol-treated HK-2 cells, accompanied by a further increased 
      autophagy level. Enhancement of PINK1/Parkin-dependent mitophagy by rapamycin 
      alleviated apoptosis and mitochondrial injury in HK-2 cells in response to 
      iohexol under ox-LDL condition. Therefore, our findings indicate that ox-LDL 
      aggravates contrast-induced injury of RTECs by increasing mitochondrial damage 
      and mitochondrial oxidative stress, which may be associated with the relative 
      insufficiency of PINK1/Parkin-dependent mitophagy.
CI  - (c) 2023 The Authors. Journal of Biochemical and Molecular Toxicology published by 
      Wiley Periodicals LLC.
FAU - Yang, Dingwei
AU  - Yang D
AUID- ORCID: 0000-0003-1675-3667
AD  - Department of Nephrology, Tianjin Hospital of Tianjin University, Tianjin, China.
FAU - Yang, Xueyan
AU  - Yang X
AD  - Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 
      China.
FAU - Chen, Sha
AU  - Chen S
AD  - Department of Nephrology, Tianjin Hospital of Tianjin University, Tianjin, China.
FAU - Lv, Meiling
AU  - Lv M
AD  - Clinical College of Orthopedics, Tianjin Medical University, Tianjin, China.
FAU - Tan, Jin
AU  - Tan J
AD  - Department of Geriatrics, Tianjin Medical University General Hospital, Tianjin 
      Geriatrics Institute, Tianjin, China.
FAU - Yang, Dingping
AU  - Yang D
AD  - Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, 
      China.
LA  - eng
GR  - TJWJ2021ZD005/The Tianjin Health Science and Technology Foundation of Tianjin 
      Municipal Health Commission/
GR  - 82070097/National Natural Science Foundation of China/
GR  - Tjyy2113/The Science and Technology Fund Project of Tianjin Hospital/
GR  - 18ZXDBSY00060/The Tianjin Science and Technology Plan Project/
PT  - Journal Article
DEP - 20230426
PL  - United States
TA  - J Biochem Mol Toxicol
JT  - Journal of biochemical and molecular toxicology
JID - 9717231
RN  - 4419T9MX03 (Iohexol)
RN  - 0 (oxidized low density lipoprotein)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.3.2.27 (Ubiquitin-Protein Ligases)
RN  - EC 2.7.- (Protein Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Humans
MH  - Iohexol/adverse effects/metabolism
MH  - *Hypercholesterolemia
MH  - Lipoproteins, LDL/metabolism
MH  - *Acute Kidney Injury/chemically induced/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Apoptosis
MH  - Epithelial Cells/metabolism
MH  - Ubiquitin-Protein Ligases/metabolism
MH  - Protein Kinases/metabolism
MH  - Sirolimus/adverse effects/metabolism
OTO - NOTNLM
OT  - CI-AKI
OT  - mitochondrial damage
OT  - mitophagy
OT  - ox-LDL
OT  - oxidative stress
EDAT- 2023/05/15 19:12
MHDA- 2023/08/11 06:43
CRDT- 2023/05/15 14:06
PHST- 2023/02/04 00:00 [revised]
PHST- 2022/09/30 00:00 [received]
PHST- 2023/04/14 00:00 [accepted]
PHST- 2023/08/11 06:43 [medline]
PHST- 2023/05/15 19:12 [pubmed]
PHST- 2023/05/15 14:06 [entrez]
AID - 10.1002/jbt.23379 [doi]
PST - ppublish
SO  - J Biochem Mol Toxicol. 2023 Aug;37(8):e23379. doi: 10.1002/jbt.23379. Epub 2023 
      Apr 26.