PMID- 29679893
OWN - NLM
STAT- MEDLINE
DCOM- 20181022
LR  - 20240327
IS  - 2213-2317 (Electronic)
IS  - 2213-2317 (Linking)
VI  - 17
DP  - 2018 Jul
TI  - Identification of homocysteine-suppressive mitochondrial ETC complex genes and 
      tissue expression profile - Novel hypothesis establishment.
PG  - 70-88
LID - S2213-2317(18)30200-3 [pii]
LID - 10.1016/j.redox.2018.03.015 [doi]
AB  - Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular 
      disease (CVD) which has been implicated in matochondrial (Mt) function 
      impairment. In this study, we characterized Hcy metabolism in mouse tissues by 
      using LC-ESI-MS/MS analysis, established tissue expression profiles for 84 
      nuclear-encoded Mt electron transport chain complex (nMt-ETC-Com) genes in 20 
      human and 19 mouse tissues by database mining, and modeled the effect of HHcy on 
      Mt-ETC function. Hcy levels were high in mouse kidney/lung/spleen/liver (24-14 
      nmol/g tissue) but low in brain/heart (~5 nmol/g). S-adenosylhomocysteine (SAH) 
      levels were high in the liver/kidney (59-33 nmol/g), moderate in lung/heart/brain 
      (7-4 nmol/g) and low in spleen (1 nmol/g). S-adenosylmethionine (SAM) was 
      comparable in all tissues (42-18 nmol/g). SAM/SAH ratio was as high as 25.6 in 
      the spleen but much lower in the heart/lung/brain/kidney/liver (7-0.6). The 
      nMt-ETC-Com genes were highly expressed in muscle/pituitary gland/heart/BM in 
      humans and in lymph node/heart/pancreas/brain in mice. We identified 15 
      Hcy-suppressive nMt-ETC-Com genes whose mRNA levels were negatively correlated 
      with tissue Hcy levels, including 11 complex-I, one complex-IV and two complex-V 
      genes. Among the 11 Hcy-suppressive complex-I genes, 4 are complex-I core 
      subunits. Based on the pattern of tissue expression of these genes, we classified 
      tissues into three tiers (high/mid/low-Hcy responsive), and defined 
      heart/eye/pancreas/brain/kidney/liver/testis/embryonic tissues as tier 1 
      (high-Hcy responsive) tissues in both human and mice. Furthermore, through 
      extensive literature mining, we found that most of the Hcy-suppressive 
      nMt-ETC-Com genes were suppressed in HHcy conditions and related with Mt complex 
      assembly/activity impairment in human disease and experimental models. We 
      hypothesize that HHcy inhibits Mt complex I gene expression leading to Mt 
      dysfunction.
CI  - Copyright (c) 2018 The Authors. Published by Elsevier B.V. All rights reserved.
FAU - Cueto, Ramon
AU  - Cueto R
AD  - Center for Metabolic Disease Research, Temple University - Lewis Katz School of 
      Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA.
FAU - Zhang, Lixiao
AU  - Zhang L
AD  - Center for Metabolic Disease Research, Temple University - Lewis Katz School of 
      Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA.
FAU - Shan, Hui Min
AU  - Shan HM
AD  - Center for Metabolic Disease Research, Temple University - Lewis Katz School of 
      Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA.
FAU - Huang, Xiao
AU  - Huang X
AD  - Center for Metabolic Disease Research, Temple University - Lewis Katz School of 
      Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA.
FAU - Li, Xinyuan
AU  - Li X
AD  - Center for Metabolic Disease Research, Temple University - Lewis Katz School of 
      Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA.
FAU - Li, Ya-Feng
AU  - Li YF
AD  - Center for Metabolic Disease Research, Temple University - Lewis Katz School of 
      Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA.
FAU - Lopez, Jahaira
AU  - Lopez J
AD  - Center for Metabolic Disease Research, Temple University - Lewis Katz School of 
      Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA.
FAU - Yang, William Y
AU  - Yang WY
AD  - Center for Metabolic Disease Research, Temple University - Lewis Katz School of 
      Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA.
FAU - Lavallee, Muriel
AU  - Lavallee M
AD  - Center for Metabolic Disease Research, Temple University - Lewis Katz School of 
      Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA.
FAU - Yu, Catherine
AU  - Yu C
AD  - Center for Metabolic Disease Research, Temple University - Lewis Katz School of 
      Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA; The Geisinger 
      Commonwealth School of Medicine, Scranton, PA, USA.
FAU - Ji, Yong
AU  - Ji Y
AD  - Key Laboratory of Cardiovascular Disease and Molecular Intervention, Nanjing 
      Medical University, Nanjing 210029, China. Electronic address: 
      yongji@njmu.edu.cn.
FAU - Yang, Xiaofeng
AU  - Yang X
AD  - Center for Metabolic Disease Research, Temple University - Lewis Katz School of 
      Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA; Department of 
      Pharmacology, Temple University - Lewis Katz School of Medicine, Philadelphia, 
      PA, USA; Thrombosis Research Center, Temple University - Lewis Katz School of 
      Medicine, Philadelphia, PA, USA; Cardiovascular Research Center, Temple 
      University - Lewis Katz School of Medicine, Philadelphia, PA, USA.
FAU - Wang, Hong
AU  - Wang H
AD  - Center for Metabolic Disease Research, Temple University - Lewis Katz School of 
      Medicine, 3500 North Broad Street, Philadelphia, PA 19140, USA; Department of 
      Pharmacology, Temple University - Lewis Katz School of Medicine, Philadelphia, 
      PA, USA; Thrombosis Research Center, Temple University - Lewis Katz School of 
      Medicine, Philadelphia, PA, USA; Cardiovascular Research Center, Temple 
      University - Lewis Katz School of Medicine, Philadelphia, PA, USA. Electronic 
      address: hongw@temple.edu.
LA  - eng
GR  - R01 HL138749/HL/NHLBI NIH HHS/United States
GR  - R01 HL108910/HL/NHLBI NIH HHS/United States
GR  - R01 HL077288/HL/NHLBI NIH HHS/United States
GR  - R01 DK113775/DK/NIDDK NIH HHS/United States
GR  - R01 HL117654/HL/NHLBI NIH HHS/United States
GR  - R01 HL130233/HL/NHLBI NIH HHS/United States
GR  - R01 HL131460/HL/NHLBI NIH HHS/United States
GR  - R01 HL082774/HL/NHLBI NIH HHS/United States
GR  - R01 HL110764/HL/NHLBI NIH HHS/United States
GR  - R01 HL132399/HL/NHLBI NIH HHS/United States
GR  - F32 HL009445/HL/NHLBI NIH HHS/United States
GR  - R01 HL067033/HL/NHLBI NIH HHS/United States
GR  - R01 HL116917/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180404
PL  - Netherlands
TA  - Redox Biol
JT  - Redox biology
JID - 101605639
RN  - 0 (Electron Transport Chain Complex Proteins)
RN  - 7LP2MPO46S (S-Adenosylmethionine)
SB  - IM
MH  - Animals
MH  - Cardiovascular Diseases/*genetics/metabolism/pathology
MH  - Electron Transport Chain Complex Proteins/*genetics/metabolism
MH  - Gene Expression Regulation/genetics
MH  - Humans
MH  - Hyperhomocysteinemia/*genetics/metabolism/pathology
MH  - Kidney/metabolism/pathology
MH  - Lung/metabolism/pathology
MH  - Mice
MH  - Mitochondria/genetics/*metabolism/pathology
MH  - Organ Specificity
MH  - Risk Factors
MH  - S-Adenosylmethionine/metabolism
MH  - Spleen/metabolism/pathology
PMC - PMC6006524
OTO - NOTNLM
OT  - Database mining
OT  - Homocysteine metabolism
OT  - Tissue expression profile
EDAT- 2018/04/22 06:00
MHDA- 2018/10/23 06:00
PMCR- 2018/04/04
CRDT- 2018/04/22 06:00
PHST- 2018/03/08 00:00 [received]
PHST- 2018/03/22 00:00 [accepted]
PHST- 2018/04/22 06:00 [pubmed]
PHST- 2018/10/23 06:00 [medline]
PHST- 2018/04/22 06:00 [entrez]
PHST- 2018/04/04 00:00 [pmc-release]
AID - S2213-2317(18)30200-3 [pii]
AID - 10.1016/j.redox.2018.03.015 [doi]
PST - ppublish
SO  - Redox Biol. 2018 Jul;17:70-88. doi: 10.1016/j.redox.2018.03.015. Epub 2018 Apr 4.