Induction of phosphoenolpyruvate carboxykinase (PEPCK) during acute acidosis and its role in acid secretion by V-ATPase-expressing ionocytes

Fumiya Furukawa, Yung Che Tseng, Sian Tai Liu, Yi Ling Chou, Ching Chun Lin, Po Hsuan Sung, Katsuhisa Uchida, Li Yih Lin, Pung Pung Hwang

研究成果: 雜誌貢獻文章

10 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)712-725
頁數14
期刊International Journal of Biological Sciences
11
發行號6
DOIs
出版狀態已發佈 - 2015 五月 1

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology
  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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