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.
Highlights
There is a sophisticated structural-functional organization in the liver acinus with regard to ammonium and glutamine metabolism (Frieg et al 2021; Gebhardt and Mecke 1983; Häussinger 1983, 1990)
Apart from established markers of glutamine synthetase (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)
glutaminase 2 (GLS2)+ hepatocytes were confined to the periportal zone, GS+ scavenger cells surrounded the central vein and both subpopulations were clearly demarked by a mid-zone constituted by GLS2−/GS− hepatocytes in rodent liver slices
Summary
There is a sophisticated structural-functional organization in the liver acinus with regard to ammonium and glutamine metabolism (Frieg et al 2021; Gebhardt and Mecke 1983; Häussinger 1983, 1990). GLS2 is activated by its product ammonium and acts as a pH-regulated mitochondrial ammonium amplifier (Häussinger 1983; Häussinger and Sies 1979; Häussinger et al 1984) This amplification is required for efficient ammonium elimination via urea synthesis in view of the low affinity of CPS1 for ammonia and the physiologically low ammonium ion concentrations in the portal blood (for review see Häussinger (1990)). Whereas periportal urea synthesis reflects a high capacity, but low affinity-system for ammonium disposal, ammonia escaping periportal urea synthesis reaches a small perivenous cell population at the acinar outflow, which removes ammonium ions with high affinity through glutamine synthesis These GS+ hepatocytes were called perivenous ‘scavenger cells’, because they remove ammonium ions, and other compounds with high affinity, before the sinusoidal blood reaches the hepatic veins (Häussinger 1990; Häussinger and Stehle 1988). The important role of these perivenous GS+ (scavenger) hepatocytes for ammonium homeostasis is
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
