We analysed the possible cellular mechanism involved in the NO action in the balance between apoptosis and cell proliferation in liver regeneration process. We determined p53, proapoptotic protein Bax, antiapoptotic Bcl-x L, proliferating cell nuclear antigen (PCNA) and apoptotic index at the early stages of regenerative process after NO increase by lipopolysaccharide-induction (LPS) of inducible-type nitric oxide synthase (iNOS) and by direct NO donor (sodium nitroprusside, SNP). Male Wistar rats were randomised in four experimental groups: sham operated control (Sh), partial hepatectomised control (PH-C), partial hepatectomised pretreated with LPS (2 mg/kg body weight, i.p.) (PH-LPS), and partial hepatectomised pretreated with SNP (2.5 mg/kg body weight, i.v. at a rate of 1 ml/h) (PH-SNP). Animals were killed 5 h post-surgery. Hepatic cytosolic iNOS showed an increase of 34% in PH-C animals with respect to Sh, and LPS-treatment increased iNOS protein levels 30% compared with PH-C. Bax and p53 protein levels showed significant increases in LPS- and SNP-treated hepatectomised rats with respect to PH-C. The apoptotic indexes were increased 75% in both, PH-LPS and PH-SNP rats versus PH-C. The increase of NO did not show any change in the proliferation process. These results suggest that NO is involved in apoptosis via p53 and Bax proteins after PH, showing a tightly regulated growth process in liver regeneration. © 2004 Elsevier B.V. All rights reserved.
Ronco, M. T., Alvarez, M. D. L., Monti, J. A., Carrillo, M. C., Pisani, G. B., Lugano, M. C., & Carnovale, C. E. (2004). Role of nitric oxide increase on induced programmed cell death during early stages of rat liver regeneration. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1690(1), 70–76. https://doi.org/10.1016/j.bbadis.2004.05.004