RESUMO
BACKGROUND: The function of prohibitin 1 (Phb1) during liver regeneration (LR) remains relatively unexplored. Our previous research identified downregulation of Phb1 in rat liver mitochondria 24 h after 70% partial hepatectomy (PHx), as determined by subcellular proteomic analysis. AIM: To investigate the potential role of Phb1 during LR. METHODS: We examined changes in Phb1 mRNA and protein levels, subcellular distribution, and abundance in rat liver during LR following 70% PHx. We also evaluated mitochondrial changes and apoptosis using electron microscopy and flow cytometry. RNA-interference-mediated knockdown of Phb1 (PHBi) was performed in BRL-3A cells. RESULTS: Compared with sham-operation control groups, Phb1 mRNA and protein levels in 70% PHx test groups were downregulated at 24 h, then upregulated at 72 and 168 h. Phb1 was mainly located in mitochondria, showed a reduced abundance at 24 h, significantly increased at 72 h, and almost recovered to normal at 168 h. Phb1 was also present in nuclei, with continuous increase in abundance observed 72 and 168 h after 70% PHx. The altered ultrastructure and reduced mass of mitochondria during LR had almost completely recovered to normal at 168 h. PHBi in BRL-3A cells resulted in increased S-phase entry, a higher number of apoptotic cells, and disruption of mitochondrial membrane potential. CONCLUSION: Phb1 may contribute to maintaining mitochondrial stability and could play a role in regulating cell proliferation and apoptosis of rat liver cells during LR.
RESUMO
BACKGROUND & OBJECTIVES: It has been reported that some proteins are released from mitochondria during liver regeneration after partial hepatectomy (PH), but the relationship between proteins release and mitochondrial permeability transition (MPT) remains unclear. We undertook this study to demonstrate the changes of mitochondrial ultrastructure and proteins release during liver regeneration and to determine the relationship between proteins release and MPT in liver regeneration in rats. METHODS: After PH and administration of cyclosporin-A (CsA, a specific inhibitor of MPT), ultrastructural morphology of mitochondria in the remnant liver were determined by electron microscopy. Catalytic activity of mitochondrial and cytosolic proteins including aspartate aminotransferase (AST) and glutamic acid dehydrogenase (GDH) was measured. RESULTS: The liver mitochondria at 24 and 72 h were quite variable in morphology and ultrastructure. The enzyme activities of AST and GDH in cytosol released from mitochondrial matrix changed significantly at 24 and 72 h. CsA can inhibit the permeability of mitochondria partly at the same time. INTERPRETATION & CONCLUSIONS: The changes of mitochondria in ultrastructure reflected the feature of MPT, and the changes of enzymes activities released from mitochondrial matrix were consistent with those of mitochondrial ultrastructure. CsA can inhibit these changes to some extent. There was a close relationship of MPT with mitochondrial ultrastructure and proteins release during liver regeneration.
