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Metabolic interactions of parenchymal hepatocytes and dividing epithelial cells in co-culture.

ABSTRACT: When parenchymal hepatocytes isolated from adult liver are co-cultured with other epithelial cells, the production of various plasma proteins by the hepatocytes is preserved for much longer than in conventional culture. This study examines some of the metabolic interactions between parenchymal hepatocytes and epithelial cells maintained in co-culture. The leakage of lactate dehydrogenase by hepatocytes co-cultured with epithelial cells was lower than in conventional hepatocyte culture. The epithelial cells have a high glycolytic rate and provide the hepatocytes with a continual supply of lactate. The [lactate] was lower in co-cultures of hepatocytes and epithelial cells than in pure epithelial cultures of similar density, suggesting lactate clearance by the hepatocytes. Alanine uptake was higher in conventional hepatocyte cultures, which lack an exogenous supply of lactate, than in parenchymal hepatocytes in co-culture. Studies with pure parenchymal hepatocytes incubated with increasing [lactate] suggest that lactate is utilized in preference to alanine as a gluconeogenic substrate by hepatocytes co-cultured with epithelial cells. Ketogenesis and carnitine palmitoyltransferase activity declined more slowly in hepatocytes co-cultured with epithelial cells than in conventional culture. It is concluded that the co-culture model has potential for long-term studies of carbohydrate and lipid metabolism.

SUBMITTER: Agius L

PROVIDER: S-EPMC1149101 | biostudies-other | 1988 May

REPOSITORIES: biostudies-other

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Project description:BackgroundClostridial co-culture containing cellulolytic and solventogenic species is a potential consolidated bioprocessing (CBP) approach for producing biochemicals and biofuels from cellulosic biomass. It has been demonstrated that the rate of cellulose utilization in the co-culture of Clostridium acetobutylicum and Clostridium cellulolyticum is improved compared to the mono-culture of C. cellulolyticum (BL 5:119-124, 1983). However, the metabolic interactions in this co-culture are not well understood. To investigate the metabolic interactions in this co-culture we dynamically characterized the physiology and microbial composition using qPCR.ResultsThe qPCR data suggested a higher growth rate of C. cellulolyticum in the co-culture compared to its mono-culture. Our results also showed that in contrast to the mono-culture of C. cellulolyticum, which did not show any cellulolytic activity under conditions similar to those of co-culture, the co-culture did show cellulolytic activity even superior to the C. cellulolyticum mono-culture at its optimal pH of 7.2. Moreover, experiments indicated that the co-culture cellulolytic activity depends on the concentration of C. acetobutylicum in the co-culture, as no cellulolytic activity was observed at low concentration of C. acetobutylicum, and thus confirming the essential role of C. acetobutylicum in improving C. cellulolyticum growth in the co-culture. Furthermore, butanol concentration of 350 mg/L was detected in the co-culture batch experiments.ConclusionThese results suggest the presence of synergism between these two species, while C. acetobutylicum metabolic activity significantly improves the cellulolytic activity in the co-culture, and allows C. cellulolyticum to survive under harsh co-culture conditions, which do not allow C. cellulolyticum to grow and metabolize cellulose independently. It is likely that C. acetobutylicum improves the cellulolytic activity of C. cellulolyticum in the co-culture through exchange of metabolites such as pyruvate, enabling it to grow and metabolize cellulose under harsh co-culture conditions.

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Metabolic interactions of parenchymal hepatocytes and dividing epithelial cells in co-culture.

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