PMID- 27607467
OWN - NLM
STAT- MEDLINE
DCOM- 20170804
LR  - 20220310
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 9
DP  - 2016
TI  - Overexpression of Catalase Enhances Benzo(a)pyrene Detoxification in Endothelial 
      Microsomes.
PG  - e0162561
LID - 10.1371/journal.pone.0162561 [doi]
LID - e0162561
AB  - We previously reported that overexpression of catalase upregulated xenobiotic- 
      metabolizing enzyme (XME) expression and diminished benzo(a)pyrene (BaP) 
      intermediate accumulation in mouse aortic endothelial cells (MAECs). Endoplasmic 
      reticulum (ER) is the most active organelle involved in BaP metabolism. To 
      examine the involvement of ER in catalase-induced BaP detoxification, we compared 
      the level and distribution of XMEs, and the profile of BaP intermediates in the 
      microsomes of wild-type and catalase transgenic endothelial cells. Our data 
      showed that endothelial microsomes were enriched in cytochrome P450 (CYP) 1A1, 
      CYP1B1 and epoxide hydrolase 1 (EH1), and contained considerable levels of 
      NAD(P)H: quinone oxidoreductase-1 (NQO1) and glutathione S-transferase-pi (GSTP). 
      Treatment of wild-type MAECs with 1muM BaP for 2 h increased the expression of 
      microsomal CYP1A1, 1B1 and NQO1 by ~300, 64 and 116%, respectively. However, the 
      same treatment did not significantly alter the expression of EH1 and GSTP. 
      Overexpression of catalase did not significantly increase EH1, but upregulated 
      BaP-induced expression of microsomal CYP1A1, 1B1, NQO1 and GSTP in the following 
      order: 1A1>NQO1>GSTP>1B1. Overexpression of catalase did not alter the 
      distribution of each of these enzymes in the microsomes. In contrast to our 
      previous report showing lower level of BaP phenols versus BaP diols/diones in the 
      whole-cell, this report demonstrated that the sum of microsomal BaP phenolic 
      metabolites were ~60% greater than that of the BaP diols/diones after exposure of 
      microsomes to BaP. Overexpression of catalase reduced the concentrations of 
      microsomal BaP phenols and diols/diones by ~45 and 95%, respectively. This 
      process enhanced the ratio of BaP phenol versus diol/dione metabolites in a 
      potent manner. Taken together, upregulation of phase II XMEs and CYP1 proteins, 
      but not EH1 in the ER might be the mechanism by which overexpression of catalase 
      reduces the levels of all the BaP metabolites, and enhances the ratio of BaP 
      phenolic metabolites versus diol/diones in endothelial microsomes.
FAU - Yang, Fang
AU  - Yang F
AD  - Department of Physiology, Meharry Medical College, Nashville, United States of 
      America.
AD  - Wuhan University School of Basic Medical Science, Wuhan, P.R. China.
FAU - Yang, Hong
AU  - Yang H
AD  - Department of Physiology, Meharry Medical College, Nashville, United States of 
      America.
FAU - Ramesh, Aramandla
AU  - Ramesh A
AD  - Department of Biochemistry and Cancer Biology, Meharry Medical College, 
      Nashville, United States of America.
FAU - Goodwin, J Shawn
AU  - Goodwin JS
AD  - Department of Biochemistry and Cancer Biology, Meharry Medical College, 
      Nashville, United States of America.
FAU - Okoro, Emmanuel U
AU  - Okoro EU
AD  - Department of Physiology, Meharry Medical College, Nashville, United States of 
      America.
FAU - Guo, ZhongMao
AU  - Guo Z
AD  - Department of Physiology, Meharry Medical College, Nashville, United States of 
      America.
LA  - eng
GR  - U54 CA163069/CA/NCI NIH HHS/United States
GR  - G12 MD007586/MD/NIMHD NIH HHS/United States
GR  - S10 RR025497/RR/NCRR NIH HHS/United States
GR  - U54 CA163072/CA/NCI NIH HHS/United States
GR  - R24 DA036420/DA/NIDA NIH HHS/United States
GR  - SC1 HL101431/HL/NHLBI NIH HHS/United States
GR  - R01 CA142845/CA/NCI NIH HHS/United States
GR  - U54 MD007593/MD/NIMHD NIH HHS/United States
PT  - Journal Article
DEP - 20160908
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Peroxides)
RN  - 0 (Xenobiotics)
RN  - 3417WMA06D (Benzo(a)pyrene)
RN  - EC 1.11.1.6 (Catalase)
RN  - EC 1.14.14.1 (Cyp1b1 protein, mouse)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1B1)
SB  - IM
MH  - Animals
MH  - Aorta/cytology
MH  - Benzo(a)pyrene/*metabolism
MH  - Catalase/*metabolism
MH  - Cytochrome P-450 CYP1A1/metabolism
MH  - Cytochrome P-450 CYP1B1/metabolism
MH  - Endoplasmic Reticulum/metabolism
MH  - Endothelial Cells/*metabolism
MH  - Inactivation, Metabolic
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Microscopy, Fluorescence
MH  - Microsomes, Liver/*metabolism
MH  - Peroxides/metabolism
MH  - Subcellular Fractions/metabolism
MH  - Xenobiotics/metabolism
PMC - PMC5015903
COIS- The authors have declared that no competing interests exist.
EDAT- 2016/09/09 06:00
MHDA- 2017/08/05 06:00
PMCR- 2016/09/08
CRDT- 2016/09/09 06:00
PHST- 2016/02/25 00:00 [received]
PHST- 2016/08/24 00:00 [accepted]
PHST- 2016/09/09 06:00 [entrez]
PHST- 2016/09/09 06:00 [pubmed]
PHST- 2017/08/05 06:00 [medline]
PHST- 2016/09/08 00:00 [pmc-release]
AID - PONE-D-16-08220 [pii]
AID - 10.1371/journal.pone.0162561 [doi]
PST - epublish
SO  - PLoS One. 2016 Sep 8;11(9):e0162561. doi: 10.1371/journal.pone.0162561. 
      eCollection 2016.