Premium
Assessment of a dual regulatory role for NO in liver regeneration after partial hepatectomy: protection against apoptosis and retardation of hepatocyte proliferation
Author(s) -
Zeini Miriam,
Hortelano Sonsoles,
Través Paqui G.,
GómezValadés Alicia G.,
Pujol Anna,
Perales José C.,
Bartrons Ramón,
Boscá Lisardo
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-3233fje
Subject(s) - liver regeneration , hepatocyte , apoptosis , nitric oxide , hepatectomy , nitric oxide synthase , regeneration (biology) , biology , liver injury , chemistry , microbiology and biotechnology , medicine , endocrinology , biochemistry , in vitro , surgery , resection
The role of hepatic nitric oxide (NO) in liver regeneration after partial hepatectomy (PH) was studied in animals carrying a nitric oxide synthase‐2 transgene under the control of the phospho(enol)pyruvate carboxykinase promoter. These mice expressed NOS‐2 in liver cells under fasting conditions. Liver mass recovery and molecular parameters related to cell proliferation were determined after PH. Preexisting hepatic NO synthesis, as well as NO delivery by NO‐donors, impaired early signaling (for example, attenuated NF‐κB activation and TNF‐α and IL‐6 release). The regenerative process was also impaired as a result of an insufficient proliferative response, but mouse survival after surgery was not compromised. However, NO exerted a protective role against apoptosis in transgenic hepatectomized mice. Local production of NO in liver cells, achieved by hydrodynamic‐based transfection with a NOS‐2‐encoding plasmid, also resulted in delayed liver recovery after PH and also protected against Fas‐mediated apoptosis. These data show that sustained presence of NO after PH exerts a dual role: attenuating liver regeneration while efficiently protecting against liver apoptosis.