PMID- 22212488
OWN - NLM
STAT- MEDLINE
DCOM- 20130123
LR  - 20211021
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Print)
IS  - 0895-8696 (Linking)
VI  - 47
IP  - 1
DP  - 2012 May
TI  - Tetrahydrocurcumin ameliorates homocysteinylated cytochrome-c mediated autophagy 
      in hyperhomocysteinemia mice after cerebral ischemia.
PG  - 128-38
LID - 10.1007/s12031-011-9695-z [doi]
AB  - High levels of homocysteine (Hcy) known as hyperhomocysteinemia (HHcy), 
      contribute to autophagy and ischemia/reperfusion injury (I/R). Previous studies 
      have shown that I/R injury and HHcy cause increased cerebrovascular permeability; 
      however, the associated mechanism remains obscure. Interestingly, during HHcy, 
      cytochome-c becomes homocysteinylated (Hcy-cyto-c). Cytochrome-c (cyto-c) 
      transports electrons and facilitates bioenergetics in the system. However, its 
      role in autophagy during ischemia/reperfusion injury is unclear. 
      Tetrahydrocurcumin (THC) is a major herbal antioxidant and anti-inflammatory 
      agent. Therefore, the objective of this study was to determine whether THC 
      ameliorates autophagy during ischemia/reperfusion injury by reducing 
      homocysteinylation of cyto-c in hyperhomocysteinemia pathological condition. To 
      test this hypothesis, we employed 8-10-week-old male cystathionine-beta-synthase 
      heterozygote knockout (CBS(+)/(-)) mice (genetically hyperhomocystemic mice). 
      Experimental group was: CBS(+)/(-), CBS(+)/(-) + THC (25 mg/kg in 0.1% DMSO dose); CBS 
      (+)/(-)/I/R, and CBS(+)/(-)/I/R + THC (25 mg/kg in 0.1% DMSO dose). Ischemia was 
      performed for 30 min and reperfusion for 72 h. THC was injected 
      intra-peritoneally (I.P.) once daily for a period of 3 days after 30 min of 
      ischemia. The infarct area was measured using 2,3,5-triphenyltetrazolium chloride 
      staining. Permeability was determined by brain edema and Evans Blue 
      extravasation. The brain tissues were analyzed for oxidative stress, matrix 
      metalloproteinase-9 (MMP-9), damage-regulated autophagy modulator (DRAM), and 
      microtubule-associated protein 1 light chain 3 (LC3) by Western blot. The mRNA 
      levels of S-adenosyl-L-homocysteine hydrolases (SAHH) and 
      methylenetetrahydrofolate reductase (MTHFR) genes were measured by quantitative 
      real-time polymerase chain reaction. Co-immunoprecipitation was used to determine 
      the homocysteinylation of cyto-c. We found that brain edema and Evans Blue 
      leakage were reduced in I/R + THC-treated groups as compared to sham-operated 
      groups along with reduced brain infarct size. THC also decreased oxidative damage 
      and ameliorated the homocysteinylation of cyto-c in-part by MMP-9 activation 
      which leads to autophagy in I/R groups as compared to sham-operated groups. This 
      study suggests a potential therapeutic role of dietary THC in cerebral ischemia.
FAU - Tyagi, Neetu
AU  - Tyagi N
AD  - Department of Physiology and Biophysics, School of Medicine, Health Sciences 
      Center, A-1115, University of Louisville, Louisville, KY 40202, USA. 
      n0tyag01@louisville.edu
FAU - Qipshidze, Natia
AU  - Qipshidze N
FAU - Munjal, Charu
AU  - Munjal C
FAU - Vacek, Jonathan C
AU  - Vacek JC
FAU - Metreveli, Naira
AU  - Metreveli N
FAU - Givvimani, Srikanth
AU  - Givvimani S
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - R01 NS051568/NS/NINDS NIH HHS/United States
GR  - NS-51568/NS/NINDS NIH HHS/United States
GR  - HL-107640/HL/NHLBI NIH HHS/United States
GR  - HL-71010/HL/NHLBI NIH HHS/United States
GR  - R01 HL107640/HL/NHLBI NIH HHS/United States
GR  - R01 HL071010/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120103
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Antioxidants)
RN  - 00U0645U03 (tetrahydrocurcumin)
RN  - 9007-43-6 (Cytochromes c)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - Animals
MH  - Antioxidants/*pharmacology
MH  - Autophagy/*drug effects/physiology
MH  - Brain Ischemia/*drug therapy/enzymology/pathology
MH  - Curcumin/*analogs & derivatives/pharmacology
MH  - Cytochromes c/metabolism/*physiology
MH  - Hyperhomocysteinemia/*drug therapy/enzymology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Reperfusion Injury/drug therapy/enzymology/pathology
PMC - PMC3609416
MID - NIHMS442616
EDAT- 2012/01/04 06:00
MHDA- 2013/01/24 06:00
PMCR- 2013/03/27
CRDT- 2012/01/04 06:00
PHST- 2011/09/29 00:00 [received]
PHST- 2011/12/08 00:00 [accepted]
PHST- 2012/01/04 06:00 [entrez]
PHST- 2012/01/04 06:00 [pubmed]
PHST- 2013/01/24 06:00 [medline]
PHST- 2013/03/27 00:00 [pmc-release]
AID - 10.1007/s12031-011-9695-z [doi]
PST - ppublish
SO  - J Mol Neurosci. 2012 May;47(1):128-38. doi: 10.1007/s12031-011-9695-z. Epub 2012 
      Jan 3.