PMID- 36763043
OWN - NLM
STAT- MEDLINE
DCOM- 20230227
LR  - 20230322
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 164
IP  - 4
DP  - 2023 Feb 11
TI  - Metabolic Characterization and Glyceraldehyde-3-Phosphate Dehydrogenase-Dependent 
      Regulation of Epithelial Sodium Channels in hPheo1 Wild-type and SDHB Knockdown 
      Cells.
LID - bqad026 [pii]
LID - 10.1210/endocr/bqad026 [doi]
AB  - Pheochromocytomas (PCC) and paragangliomas (PGL) are rare neuroendocrine tumors 
      with limited curative treatment options outside of surgical resection. Patients 
      with mutations in succinate dehydrogenase subunit B (SDHB) are at an increased 
      risk of malignant and aggressive disease. As cation channels are associated with 
      tumorigenesis, we studied the expression and activity of cation channels from the 
      Degenerin superfamily in a progenitor cell line derived from a human PCC. hPheo1 
      wild-type (WT) and SDHB knockdown (KD) cells were studied to investigate whether 
      epithelial sodium channels (ENaC) and acid-sensing ion channels (ASIC) are 
      regulated by the activity of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). 
      First, we performed targeted metabolomic studies and quantified changes in 
      glycolysis pathway intermediates and citric acid cycle intermediates using hPheo1 
      WT cells and SDHB KD cells. Next, we performed protein biochemistry and 
      electrophysiology studies to characterize the protein expression and activity, 
      respectively, of these ion channels. Our western blot experiments show both ENaC 
      alpha and ASIC1/2 are expressed in both hPheo1 WT and SDHB KD cells, with lower 
      levels of a cleaved 60 kDa form of ENaC in SDHB KD cells. Single-channel patch 
      clamp studies corroborate these results and further indicate channel activity is 
      decreased in SDHB KD cells. Additional experiments showed a more significant 
      decreased membrane potential in SDHB KD cells, which were sensitive to amiloride 
      compared to WT cells. We provide evidence for the differential expression and 
      activity of ENaC and ASIC hybrid channels in hPheo1 WT and SDHB KD cells, 
      providing an important area of investigation in understanding SDHB-related 
      disease.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the 
      Endocrine Society. All rights reserved. For permissions, please e-mail: 
      journals.permissions@oup.com.
FAU - Bala, Niharika
AU  - Bala N
AD  - Department of Physiology and Aging, University of Florida College of Medicine, 
      Gainesville, FL, USA.
FAU - Yu, Ling
AU  - Yu L
AD  - Department of Physiology and Aging, University of Florida College of Medicine, 
      Gainesville, FL, USA.
FAU - Liu, Lauren P
AU  - Liu LP
AD  - Department of Physiology and Aging, University of Florida College of Medicine, 
      Gainesville, FL, USA.
FAU - Shelton, Laura
AU  - Shelton L
AD  - bitBiome Inc., Tokyo, Japan.
FAU - Xu, Yiling
AU  - Xu Y
AD  - Department of Medicine, Division of Endocrinology & Metabolism, University of 
      Florida College of Medicine, Gainesville, FL, USA.
FAU - Ghayee, Hans K
AU  - Ghayee HK
AUID- ORCID: 0000-0001-9201-3033
AD  - Department of Medicine, Division of Endocrinology & Metabolism, University of 
      Florida College of Medicine, Gainesville, FL, USA.
AD  - Malcom Randall VA Medical Center, Gainesville, FL, USA.
FAU - Alli, Abdel A
AU  - Alli AA
AUID- ORCID: 0000-0003-4381-1172
AD  - Department of Physiology and Aging, University of Florida College of Medicine, 
      Gainesville, FL, USA.
AD  - Department of Medicine Division of Nephrology, Hypertension, and Renal 
      Transplantation, University of Florida College of Medicine, Gainesville, FL, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Epithelial Sodium Channels)
RN  - 0 (Acid Sensing Ion Channels)
RN  - EC 1.2.1.- (Glyceraldehyde-3-Phosphate Dehydrogenases)
RN  - 0 (Cations)
RN  - EC 1.3.5.1 (SDHB protein, human)
RN  - EC 1.3.99.1 (Succinate Dehydrogenase)
SB  - IM
MH  - Humans
MH  - Epithelial Sodium Channels/metabolism
MH  - Acid Sensing Ion Channels/genetics
MH  - *Pheochromocytoma
MH  - Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism
MH  - Cations/metabolism
MH  - *Adrenal Gland Neoplasms
MH  - Succinate Dehydrogenase/genetics/metabolism
OTO - NOTNLM
OT  - ASIC
OT  - ENaC
OT  - GAPDH
OT  - SDHB
OT  - degenerin superfamily
EDAT- 2023/02/11 06:00
MHDA- 2023/03/03 06:00
CRDT- 2023/02/10 10:22
PHST- 2022/08/22 00:00 [received]
PHST- 2023/02/11 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2023/02/10 10:22 [entrez]
AID - 7034155 [pii]
AID - 10.1210/endocr/bqad026 [doi]
PST - ppublish
SO  - Endocrinology. 2023 Feb 11;164(4):bqad026. doi: 10.1210/endocr/bqad026.