PMID- 28833102
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20190401
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Print)
IS  - 0021-9541 (Linking)
VI  - 233
IP  - 4
DP  - 2018 Apr
TI  - Tetrahydrocurcumin ameliorates homocysteine-mediated mitochondrial remodeling in 
      brain endothelial cells.
PG  - 3080-3092
LID - 10.1002/jcp.26145 [doi]
AB  - Homocysteine (Hcy) causes endothelial dysfunction by inducing oxidative stress in 
      most neurodegenerative disorders. This dysfunction is highly correlated with 
      mitochondrial dynamics such as fusion and fission. However, there are no 
      strategies to prevent Hcy-induced mitochondrial remodeling. Tetrahydrocurcumin 
      (THC) is an anti-inflammatory and anti-oxidant compound. We hypothesized that THC 
      may ameliorates Hcy-induced mitochondria remodeling in mouse brain endothelial 
      cells (bEnd3) cells. bEnd3 cells were exposed to Hcy treatment in the presence or 
      absence of THC. Cell viability and autophagic cell death were measured with MTT 
      and MDC staining assay. Reactive oxygen species (ROS) production was determined 
      using DCFH-DA staining by confocal microscopy. Autophagy flux was assessed using 
      a conventional GFP-microtubule-associated protein 1 light chain 3 (LC3) dot 
      assay. Interaction of phagophore marker LC-3 with mitochondrial receptor NIX was 
      observed by confocal imaging. Mitochondrial fusion and fission were evaluated by 
      western blot and RT-PCR. Our results demonstrated that Hcy resulted in cell 
      toxicity in a dose-dependent manner and supplementation of THC prevented the 
      detrimental effects of Hcy on cell survival. Furthermore, Hcy also upregulated 
      fission marker (DRP-1), fusion marker (Mfn2), and autophagy marker (LC-3). 
      Finally, we observed that Hcy activated mitochondrial specific phagophore marker 
      (LC-3) and co-localized with the mitochondrial receptor NIX, as viewed by 
      confocal microscopy. Pretreatment of bEnd3 with THC (15 muM) ameliorated 
      Hcy-induced oxidative damage, mitochondrial fission/fusion, and mitophagy. Our 
      studies strongly suggest that THC has beneficial effects on mitochondrial 
      remodeling and could be developed as a potential therapeutic agent against 
      hyperhomocysteinemia (HHcy) induced mitochondrial dysfunction.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Vacek, Jonathan C
AU  - Vacek JC
AD  - Department of Physiology, School of Medicine, Health Sciences Center, University 
      of Louisville, Louisville, Kentucky.
FAU - Behera, Jyotirmaya
AU  - Behera J
AD  - Department of Physiology, School of Medicine, Health Sciences Center, University 
      of Louisville, Louisville, Kentucky.
FAU - George, Akash K
AU  - George AK
AD  - Department of Physiology, School of Medicine, Health Sciences Center, University 
      of Louisville, Louisville, Kentucky.
FAU - Kamat, Pradip K
AU  - Kamat PK
AD  - Department of Physiology, School of Medicine, Health Sciences Center, University 
      of Louisville, Louisville, Kentucky.
FAU - Kalani, Anuradha
AU  - Kalani A
AD  - Department of Physiology, School of Medicine, Health Sciences Center, University 
      of Louisville, Louisville, Kentucky.
FAU - Tyagi, Neetu
AU  - Tyagi N
AUID- ORCID: 0000-0003-0285-5072
AD  - Department of Physiology, School of Medicine, Health Sciences Center, University 
      of Louisville, Louisville, Kentucky.
LA  - eng
GR  - R01 AR067667/AR/NIAMS NIH HHS/United States
GR  - R01 HL107640/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20171114
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 00U0645U03 (tetrahydrocurcumin)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Autophagy/drug effects
MH  - Brain
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Curcumin/*analogs & derivatives/pharmacology
MH  - Cytoprotection/drug effects
MH  - Endothelial Cells/drug effects/*metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Homocysteine/*toxicity
MH  - Intracellular Space/metabolism
MH  - Mice
MH  - Mitochondria/drug effects/*metabolism
MH  - Mitochondrial Dynamics/drug effects
MH  - Mitochondrial Proteins/metabolism
MH  - Models, Biological
MH  - Reactive Oxygen Species/metabolism
PMC - PMC6035784
MID - NIHMS903889
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - curcumin
OT  - mitochondria biogenesis
OT  - reactive oxygen species
COIS- Conflict of Interest: Authors have declared no conflict of interest.
EDAT- 2017/08/24 06:00
MHDA- 2018/12/12 06:00
PMCR- 2019/04/01
CRDT- 2017/08/24 06:00
PHST- 2016/11/08 00:00 [received]
PHST- 2017/08/08 00:00 [accepted]
PHST- 2017/08/24 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2017/08/24 06:00 [entrez]
PHST- 2019/04/01 00:00 [pmc-release]
AID - 10.1002/jcp.26145 [doi]
PST - ppublish
SO  - J Cell Physiol. 2018 Apr;233(4):3080-3092. doi: 10.1002/jcp.26145. Epub 2017 Nov 
      14.