PMID- 32251675
OWN - NLM
STAT- MEDLINE
DCOM- 20201223
LR  - 20211204
IS  - 1873-2968 (Electronic)
IS  - 0006-2952 (Linking)
VI  - 177
DP  - 2020 Jul
TI  - Procyanidin B2 gallate regulates TNF-alpha production from T cells through inhibiting 
      glycolytic activity via mTOR-HIF-1 pathway.
PG  - 113952
LID - S0006-2952(20)30180-5 [pii]
LID - 10.1016/j.bcp.2020.113952 [doi]
AB  - Procyanidins are polyphenols with antioxidant, anti-obesity, and 
      anti-inflammatory properties. Procyanidin B2 (PCB2) gallate; specifically, PCB2 
      3,3''-di-O-gallate (PCB2DG), inhibits cytokine production in T cells. However, the 
      molecular interactions and partners of PCB2DG underlying this suppression of 
      cytokine production are unclear. The present study aimed to elucidate mechanisms 
      underlying regulation of tumor necrosis factor (TNF)-alpha production by PCB2DG. We 
      found that production of TNF-alpha and glycolytic activity in activated CD4(+) T 
      cells were suppressed by PCB2DG treatment. The inhibition of TNF-alpha production was 
      found to be mediated by mammalian target of rapamycin (mTOR) and hypoxia 
      inducible factor 1 (HIF-1) pathway, as PCB2DG suppressed the expression of 
      HIF-1alpha, p-mTOR, and p-p70S6K (a downstream of the mTOR complex, mTORC1). 
      Moreover, suppression of TNF-alpha production was mediated by regulation of the 
      glycolytic enzyme lactate dehydrogenase at the posttranscriptional level. These 
      results suggest that PCB2DG regulates TNF-alpha production by inhibiting glycolytic 
      activity via the mTOR-HIF-1 pathway.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Endo, Katsunori
AU  - Endo K
AD  - Graduate School of Science and Technology, Department of Agriculture, Division of 
      Food Science and Biotechnology, Shinshu University, Minami-minowa, Kami-ina, 
      Nagano 399-4598, Japan.
FAU - Matsui, Rina
AU  - Matsui R
AD  - Graduate School of Science and Technology, Department of Agriculture, Division of 
      Food Science and Biotechnology, Shinshu University, Minami-minowa, Kami-ina, 
      Nagano 399-4598, Japan.
FAU - Sugiyama, Momona
AU  - Sugiyama M
AD  - Graduate School of Science and Technology, Department of Agriculture, Division of 
      Food Science and Biotechnology, Shinshu University, Minami-minowa, Kami-ina, 
      Nagano 399-4598, Japan.
FAU - Asami, Takuya
AU  - Asami T
AD  - Graduate School of Science and Technology, Department of Agriculture, Division of 
      Food Science and Biotechnology, Shinshu University, Minami-minowa, Kami-ina, 
      Nagano 399-4598, Japan.
FAU - Inaba, Chihiro
AU  - Inaba C
AD  - Graduate School of Science and Technology, Department of Agriculture, Division of 
      Food Science and Biotechnology, Shinshu University, Minami-minowa, Kami-ina, 
      Nagano 399-4598, Japan.
FAU - Kobayashi, Shuhei
AU  - Kobayashi S
AD  - Graduate School of Science and Technology, Department of Agriculture, Division of 
      Food Science and Biotechnology, Shinshu University, Minami-minowa, Kami-ina, 
      Nagano 399-4598, Japan.
FAU - Makabe, Hidefumi
AU  - Makabe H
AD  - Graduate School of Science and Technology, Department of Agriculture, Division of 
      Food Science and Biotechnology, Shinshu University, Minami-minowa, Kami-ina, 
      Nagano 399-4598, Japan; Institute for Biomedical Sciences, Interdisciplinary 
      Cluster for Cutting Edge, Division of Innovative Biomolecular Science, Shinshu 
      University, 8304 Minami-minowa Kami-ina, Nagano 399-4598, Japan.
FAU - Tanaka, Sachi
AU  - Tanaka S
AD  - Graduate School of Science and Technology, Department of Agriculture, Division of 
      Food Science and Biotechnology, Shinshu University, Minami-minowa, Kami-ina, 
      Nagano 399-4598, Japan. Electronic address: tanakasa@shinshu-u.ac.jptana.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200403
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Biflavonoids)
RN  - 0 (Cytokines)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Proanthocyanidins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 29106-49-8 (procyanidin B2)
RN  - 8R1V1STN48 (Catechin)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Biflavonoids/chemical synthesis/chemistry/*pharmacology
MH  - Blotting, Western
MH  - CD4-Positive T-Lymphocytes/cytology/drug effects/metabolism
MH  - Catechin/chemical synthesis/chemistry/*pharmacology
MH  - Cells, Cultured
MH  - Cytokines/biosynthesis/genetics
MH  - Glycolysis/*drug effects
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Mice, Inbred C57BL
MH  - Proanthocyanidins/chemical synthesis/chemistry/*pharmacology
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/drug effects
MH  - T-Lymphocytes/cytology/*drug effects/metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/genetics
OTO - NOTNLM
OT  - Glycolysis
OT  - HIF-1
OT  - Procyanidin B2
OT  - TNF-alpha
OT  - mTOR
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/04/07 06:00
MHDA- 2020/12/29 06:00
CRDT- 2020/04/07 06:00
PHST- 2020/01/22 00:00 [received]
PHST- 2020/04/01 00:00 [accepted]
PHST- 2020/04/07 06:00 [pubmed]
PHST- 2020/12/29 06:00 [medline]
PHST- 2020/04/07 06:00 [entrez]
AID - S0006-2952(20)30180-5 [pii]
AID - 10.1016/j.bcp.2020.113952 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2020 Jul;177:113952. doi: 10.1016/j.bcp.2020.113952. Epub 2020 
      Apr 3.