Characterization of the scavenger cell proteome in mouse and rat liver

Abstract

The structural-functional organization of ammonia and glutamine metabolism in the liver acinus involves highly specialized hepatocyte subpopulations like glutamine synthetase (GS) expressing perivenous hepatocytes (scavenger cells). However, this cell population has not yet been characterized extensively regarding expression of other genes and potential subpopulations. This was investigated in the present study by proteome profiling of periportal GS-negative and perivenous GS-expressing hepatocytes from mouse and rat. Apart from established markers of GS+ hepatocytes such as glutamate/aspartate transporter II (GLT1) or ammonium transporter Rh type B (RhBG), we identified novel scavenger cell-specific proteins like basal transcription factor 3 (BTF3) and heat-shock protein 25 (HSP25). Interestingly, BTF3 and HSP25 were heterogeneously distributed among GS+ hepatocytes in mouse liver slices. Feeding experiments showed that RhBG expression was increased in livers from mice fed with high protein diet compared to standard chow. While spatial distributions of GS and carbamoylphosphate synthetase 1 (CPS1) were unaffected, periportal areas constituted by glutaminase 2 (GLS2)-positive hepatocytes were enlarged or reduced in response to high or low protein diet, respectively. The data suggest that the population of perivenous GS+ scavenger cells is heterogeneous and not uniform as previously suggested which may reflect a functional heterogeneity, possibly relevant for liver regeneration.

Asparagine protects pericentral hepatocytes during acute liver injury

“…To gain insights into the metabolism of this highly specialized population of GLUL-positive (GLUL+) hepatocytes, we developed a fluorescence-activated cell sorting (FACS)based protocol to separate GLUL+ and GLUL-negative (GLUL-) hepatocytes from livers of 10-12-weeks old male C57BL/6J mice (Figure 1B and Supplemental Figure 1A). RNA and protein analyses from these FACS-sorted cells revealed that GLUL+ hepatocytes express several enzymes and transporters required for optimal glutamine production, such as the ammonium transporter Rhesus type glycoprotein B (RHBG), the glutamate/aspartate transporter (SLC1A2), the glutamate transporter (SLC1A4), the glutamine transporter (SLC1A5) and the ornithine aminotransferase (OAT) (Figure 1C-D), as previously described (13)(14)(15)(16). We then asked what could be the fate of newly synthesized pericentral glutamine.…”

Unveiling the power of microenvironment in liver regeneration: an in-depth overview

“…Hepatocytes in the PV region decompose glutamine to produce partial ammonia ( Gls2 gene expression advantage). Hepatocytes in the CV region mainly synthesize glutamine ( Glul gene expression advantage) ( Hakvoort et al, 2017 ; Paluschinski et al, 2021 ). It is important to note that the synthesis of glutamine is also a significant detoxification pathway for ammonia to some extent.…”