Protein metabolism and survival of rat hepatocytes in early culture

Rat hepatocytes, cultured in a serum- and hormone-free medium on a substratum of adsorbed fibronectin, are in negative protein balance throughout the first 24 h of culture. The rate of protein loss at all times equals the difference between the high rate of protein degradation and the low rate of protein synthesis. A continuous decline in the rate of protein degradation gradually reduces the loss of protein, probably the result of medium conditioning as well as progressive culture deterioration. Inhibition of lysosomal protein degradation by amino acids and the protease inhibitor, leupeptin, reduces the protein loss considerably, but does not prevent cell death. The protein balance per se thus does not seem to be the limiting factor for the survival of cultured hepatocytes.