Apoptotic and proliferating hepatocytes differ in prothymosin alpha expression and cell localization

Abstract

Prothymosin alpha is an acidic protein, reported to be involved in cell proliferation and apoptosis, although its precise function in both processes are still unknown. Due to the importance of these processes in the pathogenesis of hepatic diseases and the need to understand the molecular mechanisms underlying these diseases we aimed to investigate the behavior of this protein in liver growth and apoptosis, in two models of hepatocytes in culture. Prothymosin alpha expression varied throughout the hepatocyte cell cycle, according to its progression. Proliferating hepatocytes showed increased expression of the protein, while apoptotic ones showed decreased levels. The subcellular location of prothymosin alpha differed according to the different phases of the cell cycle. Thus, it appeared with a stippled and widely dispersed pattern throughout the nucleus in quiescent and proliferating hepatocytes, while it became cytoplasmic in mitotic and late apoptotic cells. These results are in agreement with the idea that high levels of prothymosin alpha need to be present in the nucleus for proliferation, and programmed cell death requires low levels of prothymosin alpha outside of the nucleus. The differences in prothymosin alpha expression and localization during hepatocyte proliferation and apoptosis suggest that this protein may have a pleiotropic function that depends not only on its availability but also on its various localizations in different subcellular compartments.