[The role of mitochondrial gluconeogenesis in de novo serine synthesis in mouse hepatocytes under high-selenium conditions].

Authors

Jianrong Wang, Qin Wang, Feng Han, Xuesong Xiang, Yiqun Liu, Zhenwu Huang

Published in

Wei sheng yan jiu = Journal of hygiene research. Volume 55. Issue 3. Pages 512-530.

Abstract

To investigate the source of 3-PG in mouse normal hepatocytes(AML12) under high-Se condition, and to clarify whether the gluconeogenic pathway contributes to SSP activation.
AML12 cells were divided into four groups: control group, high-Se group(Se), siPCK2 group(siPCK2), and high-Se group with siPCK2 group(Se+siPCK2). Mitochondrial phosphoenolpyruvate carboxykinase(PCK2) expression was silenced by siRNA. Western blotting was employed to examine the expression of gluconeogenic enzymes(PCK1, PCK2, G-6-Pase), serine biosynthesis and metabolism-related enzymes(PHGDH, PSAT1, SHMT1, MTHFR, MS), selenoproteins(SELENOP, GPX1), and insulin signaling-related proteins(PI3K, AKT, mTOR, AMPK).
Compared with the control group, Se treatment significantly increased the expression of PCK2(P<0.05) and G-6-Pase(P<0.05). Key enzymes involved in serine biosynthesis and metabolism-related enzymes(PHGDH, PSAT1, SHMT1, MTHFR, MS) as well as selenoproteins(SELENOP, GPX1) were also upregulated(P<0.05). AMPK and its phosphorylated form(AMPK S496) were activated(P<0.05), while the PI3K-AKT-mTOR signaling components, including mTOR S2448, AKT S473, and AKT T308, were markedly suppressed(P<0.05). Interference with PCK2 significantly reversed the Se-induced upregulation of gluconeogenic and serine biosynthesis and metabolism-related enzymes(P<0.05) and partially restored PI3K and AKT expression(P<0.05), though AMPK and mTOR signaling remained incompletely recovered. PCK1 expression showed no significant difference among all groups.
Under high-Se conditions, gluconeogenesis-particularly PCK2-mediated mitochondrial gluconeogenesis-is the predominant source of 3-PG required for de novo serine synthesis in AML12 hepatocytes.

PMID:
42394338
Bibliographic data and abstract were imported from PubMed on 03 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.