Community Action Needed: Please respond to the NIH RFI
ZFIN ID: ZDB-PUB-150523-4
Induction of Phosphoenolpyruvate Carboxykinase (PEPCK) during Acute Acidosis and Its Role in Acid Secretion by V-ATPase-Expressing Ionocytes
Furukawa, F., Tseng, Y.C., Liu, S.T., Chou, Y.L., Lin, C.C., Sung, P.H., Uchida, K., Lin, L.Y., Hwang, P.P.
Date: 2015
Source: International journal of biological sciences   11(6): 712-725 (Journal)
Registered Authors:
Keywords: Gluconeogenesis, PEPCK, V-ATPase, acid-base regulation, glutamine
MeSH Terms:
  • Acidosis/enzymology*
  • Acidosis/genetics
  • Acidosis/metabolism
  • Amino Acids/metabolism
  • Ammonium Compounds/metabolism
  • Animals
  • Citric Acid Cycle
  • Gene Knockdown Techniques
  • Glucose/metabolism
  • Glutamate Dehydrogenase/metabolism
  • Glutaminase/metabolism
  • Malates/metabolism
  • Phosphoenolpyruvate Carboxykinase (ATP)/genetics
  • Phosphoenolpyruvate Carboxykinase (ATP)/metabolism
  • Phosphoenolpyruvate Carboxykinase (ATP)/physiology*
  • Protons
  • RNA, Messenger/analysis
  • RNA, Messenger/metabolism
  • Stress, Physiological
  • Vacuolar Proton-Translocating ATPases/metabolism*
  • Vacuolar Proton-Translocating ATPases/physiology
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/metabolism*
  • Zebrafish Proteins/physiology
PubMed: 25999794 Full text @ Int. J. Biol. Sci.
Vacuolar-Type H(+)-ATPase (V-ATPase) takes the central role in pumping H(+) through cell membranes of diverse organisms, which is essential for surviving acid-base fluctuating lifestyles or environments. In mammals, although glucose is believed to be an important energy source to drive V-ATPase, and phosphoenolpyruvate carboxykinase (PEPCK), a key enzyme for gluconeogenesis, is known to be activated in response to acidosis, the link between acid secretion and PEPCK activation remains unclear. In the present study, we used zebrafish larva as an in vivo model to show the role of acid-inducible PEPCK activity in glucose production to support higher rate of H(+) secretion via V-ATPase, by utilizing gene knockdown, glucose supplementation, and non-invasive scanning ion-selective electrode technique (SIET). Zebrafish larvae increased V-ATPase-mediated acid secretion and transiently expression of Pck1, a zebrafish homolog of PEPCK, in response to acid stress. When pck1 gene was knocked down by specific morpholino, the H(+) secretion via V-ATPase decreased, but this effect was rescued by supplementation of glucose into the yolk. By assessing changes in amino acid content and gene expression of respective enzymes, glutamine and glutamate appeared to be the major source for replenishment of Krebs cycle intermediates, which are subtracted by Pck1 activity. Unexpectedly, pck1 knockdown did not affect glutamine/glutamate catalysis, which implies that Pck1 does not necessarily drive this process. The present study provides the first in vivo evidence that acid-induced PEPCK provides glucose for acid-base homeostasis at an individual level, which is supported by rapid pumping of H(+) via V-ATPase at the cellular level.