PMID- 34759830
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220110
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 12
DP  - 2021
TI  - Augmented Liver Uptake of the Membrane Voltage Sensor Tetraphenylphosphonium 
      Distinguishes Early Fibrosis in a Mouse Model.
PG  - 676722
LID - 10.3389/fphys.2021.676722 [doi]
LID - 676722
AB  - Mitochondrial (mito-) oxidative phosphorylation (OxPhos) is a critical 
      determinant of cellular membrane potential/voltage. Dysregulation of OxPhos is a 
      biochemical signature of advanced liver fibrosis. However, less is known about 
      the net voltage of the liver in fibrosis. In this study, using the radiolabeled 
      [(3)H] voltage sensor, tetraphenylphosphonium (TPP), which depends on membrane 
      potential for cellular uptake/accumulation, we determined the net voltage of the 
      liver in a mouse model of carbon tetrachloride (CCl(4))-induced hepatic fibrosis. 
      We demonstrated that the liver uptake of (3)H-TPP significantly increased at 4 
      weeks of CCl(4)-administration (6.07 +/- 0.69% ID/g, p < 0.05) compared with 6 
      weeks (4.85 +/- 1.47% ID/g) and the control (3.50 +/- 0.22% ID/g). Analysis of the 
      fibrosis, collagen synthesis, and deposition showed that the increased (3)H-TPP 
      uptake at 4 weeks corresponds to early fibrosis (F1), according to the METAVIR 
      scoring system. Biodistribution data revealed that the (3)H-TPP accumulation is 
      significant in the fibrogenic liver but not in other tissues. Mechanistically, 
      the augmentation of the liver uptake of (3)H-TPP in early fibrosis concurred with 
      the upregulation of mito-electron transport chain enzymes, a concomitant increase 
      in mito-oxygen consumption, and the activation of the AMPK-signaling pathway. 
      Collectively, our results indicate that mito-metabolic response to hepatic insult 
      may underlie the net increase in the voltage of the liver in early fibrosis.
CI  - Copyright (c) 2021 Pandita, Mezey and Ganapathy-Kanniappan.
FAU - Pandita, Himanshi
AU  - Pandita H
AD  - Division of Interventional Radiology, Russell H. Morgan Department of Radiology 
      and Radiological Science, The Johns Hopkins University School of Medicine, 
      Baltimore, MD, United States.
FAU - Mezey, Esteban
AU  - Mezey E
AD  - Division of Gastroenterology and Hepatology, Department of Medicine, The Johns 
      Hopkins University School of Medicine, Baltimore, MD, United States.
FAU - Ganapathy-Kanniappan, Shanmugasundaram
AU  - Ganapathy-Kanniappan S
AD  - Division of Interventional Radiology, Russell H. Morgan Department of Radiology 
      and Radiological Science, The Johns Hopkins University School of Medicine, 
      Baltimore, MD, United States.
LA  - eng
PT  - Journal Article
DEP - 20211025
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
EIN - Front Physiol. 2021 Dec 22;12:830151. PMID: 35002786
PMC - PMC8573124
OTO - NOTNLM
OT  - carbon tetrachloride
OT  - electron transport chain
OT  - liver fibrosis
OT  - liver voltage
OT  - membrane-voltage sensor
OT  - mitochondrial respiration
OT  - tetraphenylphosphonium (TPP)
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/11/12 06:00
MHDA- 2021/11/12 06:01
PMCR- 2021/10/25
CRDT- 2021/11/11 06:53
PHST- 2021/03/05 00:00 [received]
PHST- 2021/09/21 00:00 [accepted]
PHST- 2021/11/11 06:53 [entrez]
PHST- 2021/11/12 06:00 [pubmed]
PHST- 2021/11/12 06:01 [medline]
PHST- 2021/10/25 00:00 [pmc-release]
AID - 10.3389/fphys.2021.676722 [doi]
PST - epublish
SO  - Front Physiol. 2021 Oct 25;12:676722. doi: 10.3389/fphys.2021.676722. eCollection 
      2021.