PubMed Health⌕ Search

Biomedical subjects

A M Diehl

Publications and source records attributed to A M Diehl.

At least 19 recordsLinked to original sources
PubMed1997

Obesity increases sensitivity to endotoxin liver injury: implications for the pathogenesis of steatohepatitis.

Genetically obese fatty/fatty rats and obese/obese mice exhibit increased sensitivity to endotoxin hepatotoxicity, quickly developing steatohepatitis after exposure to low doses of lipopolysaccharide (LPS). Among obese animals, females are more sensitive to endotoxin liver injury than males. LPS induction of tumor necrosis factor alpha (TNF alpha), the proven affecter of endotoxin liver injury, is no greater in the livers, white adipose tissues, or sera of obese animals than in those of lean controls. Indeed, the lowest serum concentrations of TNF occur in female obese rodents, which exhibit the most endotoxin-induced liver injury. Several cytokines that modulate the biological activity of TNF are regulated abnormally in the livers of obese animals. After exposure to LPS, mRNA of interferon gamma, which sensitizes hepatocytes to TNF toxicity, is overexpressed, and mRNA levels of interleukin 10, a TNF inhibitor, are decreased. The phagocytic activity of liver macrophages and the hepatic expression of a gene encoding a macrophage-specific receptor are also decreased in obesity. This new animal model of obesity-associated liver disease demonstrates that hepatic macrophage dysfunction occurs in obesity and suggests that this might promote steatohepatitis by sensitizing hepatocytes to endotoxin.

Animals↗
PubMed1997

Kupffer cell depletion abolishes induction of interleukin-10 and permits sustained overexpression of tumor necrosis factor alpha messenger RNA in the regenerating rat liver.

Tumor necrosis factor alpha (TNF), initiates a cytokine cascade that promotes hepatocyte proliferation after 70% partial hepatectomy (PH) but the mechanisms regulating TNF production after PH are unknown. We previously reported that gadolinium chloride (GdCl), an agent that depletes the liver of phagocytically active Kupffer cells, enhances hepatic expression of TNF messenger RNA (mRNA) and promotes liver regeneration after subsequent PH. This suggests that GdCl interferes with Kupffer cell mechanisms that normally constrain TNF production after PH. To evaluate this, the pre- and post-PH expression of TNF, TNF-inducible cytokines (interleukin [IL]-1, IL-6) and cytokines (transforming growth factor [TGF] beta 1 and IL-10) that down-regulate TNF were compared in controls and GdCl-treated rats. In controls, TNF, IL-1, IL-6, and IL-10 increase within 3 hours after PH, whereas TGF-beta 1 is induced much later (> 24 hours after PH). GdCl causes sustained overexpression of TNF mRNA and transient overexpression of circulating TNF protein after PH; both TNF-inducible cytokines are also relatively overexpressed. Cytokines that down-regulate TNF are effected differentially by GdCl. Regenerative induction of IL-10 is abolished but TGF-beta 1 induction is unaltered. Because IL-10 is known to shorten the half-life of TNF mRNA, these results suggest that Kupffer cell production of IL-10 is an important mechanism that down-regulates TNF production during liver regeneration.

Animals↗
PubMed1996

Tumor necrosis factor alpha promotes nuclear localization of cytokine-inducible CCAAT/enhancer binding protein isoforms in hepatocytes.

Hepatocytes were cultured in the presence of recombinant tumor necrosis factor (TNF) alpha or mutated TNF alpha peptides that specifically activate either p55 or p75 TNF receptors to determine if TNF alpha can activate cytokine-inducible CCAAT/enhancer binding protein (C/EBP) isoforms by post-transcriptional mechanisms that are initiated by TNF receptors. Within 5-10 min after treatment with any of these agents, nuclear concentrations of C/EBP beta and C/EBP delta double and remain 2-4-fold greater than control cultures for 30 min (p < 0.01). Consistent with these results, gel mobility shift assays demonstrate 3-fold increased nuclear C/EBP beta- and C/EBP delta-DNA binding activity in TNF alpha-treated cells, and immunocytochemistry confirms rapid redistribution of these C/EBP isoforms into the nucleus. In contrast, mRNA and whole cell protein concentrations of C/EBP beta and delta are not altered by TNF alpha exposure, and nuclear concentrations of another C/EBP isoform, C/EBP alpha, are decreased by 80%. This novel evidence that TNF alpha initiates post-transcriptional activation of cytokine-inducible C/EBP isoforms identifies a mechanism that enables hepatocytes to respond immediately to inflammatory stress.

Amino Acid Sequence↗
PubMed1996

Adenovirus-mediated transfer of CCAAT/enhancer-binding protein-alpha identifies a dominant antiproliferative role for this isoform in hepatocytes.

CCAAT/enhancer-binding protein (C/EBP) isoforms are thought to be important regulators of the hepatocyte phenotype. However, the specific physiological roles of different isoforms are poorly understood because hepatocytes express multiple C/EBPs, and various isoforms have overlapping functions. To identify the functions of C/EBPalpha in mature hepatocytes, replication-defective adenovirus vectors were used to efficiently and homogeneously overexpress the mouse C/EBPalpha gene in a SV40 virus-conditionally transformed rat hepatocyte line that can be induced to express C/EBPbeta and C/EBPdelta but that has little endogenous C/EBPalpha expression. Hepatocytes were infected with a recombinant adenovirus vector carrying the cDNA for C/EBPalpha driven by Rous sarcoma virus promoter elements (AdCEBPalpha) or a similar vector carrying the Escherichia coli lacZ gene (Adbetagal). Staining for beta-galactosidase demonstrated an infection efficiency of 100% at a multiplicity of infection of 25 plaque-forming units/cell and persistence of foreign gene expression for at least 9 days. Cultures infected with AdCEBPalpha had 50-fold higher levels of C/EBPalpha mRNA and protein than those infected with Ad-beta-gal, but similar expression of C/EBP-beta. Infection with AdCEBPalpha inhibited proliferation in cells expressing little C/EBPbeta, even when proliferation was driven by the SV40 transforming antigen, and also blunted mitogenic induction of the c-myc proto-oncogene in nontransformed cells with high levels of C/EBPbeta. Although overexpression of C/EBPalpha consistently increased C/EBPalpha DNA binding activity, it was not sufficient for albumin expression. Infection with AdCEBPalpha only increased albumin mRNA levels in nontransformed cells that also expressed relatively high levels of C/EBPbeta. Thus, in hepatocytes, C/EBPalpha has a dominant antiproliferative function, but must interact with other factors to regulate hepatocyte-specific gene expression.

Adenoviridae↗
PubMed1996

Liver regeneration 3: Regulation of signal transduction during liver regeneration.

The liver has a tremendous capacity to regenerate. For example, after extensive hepatic resection, remaining hepatocytes proliferate to restore the mass of the organ within days to weeks. This proliferative response is fascinating because hepatocytes rarely replicate in the healthy adult liver. Instead, these cells perform highly specialized functions and exemplify mature, terminally differentiated cells. Therefore it is somewhat surprising that the liver can repopulate while performing its many obligate, organ-specific functions. Study of the regenerating liver remnant after partial hepatectomy has helped to delineate mechanisms that regulate proliferation and liver-specific functions in individual hepatocytes, as well as those that coordinate the behaviors of different liver cell populations to balance organ growth and tissue-specific gene expression. Hence, this review will focus on inter- and intracellular signals that regulate the hepatocyte phenotype after PH.

Animals↗
PubMed1996

Gadolinium chloride alters the acinar distribution of phagocytosis and balance between pro- and anti-inflammatory cytokines.

Gadolinium chloride (GdCl3) is commonly used to deplete the liver of Kupffer cells (KC) and has been shown to decrease hepatic phagocytic activity and to abolish hepatic expression of certain KC-specific antigens. However, the exact fate of the KCs after GdCl3 treatment remains unclear. To determine if GdCl3 actually decreases the total number of KCs in the liver, we labeled phagocytically-active KC by administering fluorescent-labeled latex beads to rats treated with either normal saline or GdCl3. Total hepatic fluorescence and the distribution of fluorescence within liver acini were evaluated by intravital microscopy. Hepatic mRNA levels of KCR, a KC-specific gene product, and Pu-1, a ubiquitous monocyte gene product, were assessed by Northern blot analysis, and differences in the expression of pro-inflammatory (tumor necrosis factor (TNF)-alpha) and anti-inflammatory (interleukin (IL)-10) cytokines were assessed by reverse-transcriptase polymerase chain reaction (RT-PCR). Our results indicate that GdCl3 does not significantly reduce the number of phagocytically active cells in the liver, but alters the acinar distribution of these cells and may provoke a switch in the KC phenotype such that these cells no longer express KCR or IL-10. GdCl3 pretreatment inhibited stress-related induction of IL-10, but failed to down-regulate expression of TNF-alpha. This phenotypic change is likely to have important consequences because it permits relative overexpression of TNF-alpha.

Animals↗
PubMed1996

Review: regulation of liver regeneration by pro-inflammatory cytokines.

The liver has tremendous regenerative capacity. This distinguishes it from other vital organs (e.g. the brain, heart and lungs) that cannot replace functional tissue once it has been destroyed. Although hepatocytes rarely proliferate in the healthy adult liver, virtually all surviving hepatocytes replicate at least once after 70% partial hepatectomy. Therefore, partial liver resection has been used to characterize mechanisms that regulate liver regeneration. Residual hepatocytes up-regulate both proliferative and liver-specific gene expression in order to preserve tissue specific function. In addition, hepatocyte proliferation is tightly co-ordinated to complement regenerative responses in hepatic non-parenchymal cells (e.g. endothelia, biliary epithelia, stellate and Kupffer cells), so that the entire organ can be reconstituted within days. Studies with neutralizing antibodies to tumour necrosis factor-alpha (TNF) clearly demonstrate that, after partial hepatectomy, TNF promotes liver cell proliferation. The present review focuses on the regulation of the hepatocyte proliferative response by pro-inflammatory cytokines.

Cell Division↗
PubMed1996

Alcohol and cytokine-inducible transcription factors.

Cytokines, such as TNF alpha, modulate the behavior of many cells by regulating the expression of a wide array of genes. When a cytokine binds to its receptor on the cell surface, the receptor becomes activated and activates signal transduction cascades. These cascades typically involve a series of phosphorylation reactions that lead to sequential activation of various kinases. The targets of these kinases include DNA binding proteins that regulate the transcription of target genes. The activity of DNA binding proteins, such as c-Jun and NF-kappa B, titrates the transcriptional activity of cytokine-regulated genes. Both acute and chronic alcohol consumption of ethanol increase hepatic expression of TNF alpha. After acute ethanol consumption, this is associated with increased induction of several TNF-dependent regenerative events, including the activation of c-Jun and increased binding activity of NF-kappa B. However, chronic consumption of ethanol appears to impede TNF alpha signaling in the liver because it attenuates the increases in c-JUN activity and NF-kappa B binding, which normally follow partial hepatectomy. These results suggest that one mechanism by which ethanol influences liver cell behavior is by influencing local expression of TNF alpha and changing the activity of TNF-regulated transcription factors.

Alcohol Drinking↗
PubMed1996

Kupffer cell depletion by gadolinium chloride enhances liver regeneration after partial hepatectomy in rats.

Although previous work suggests that tumor necrosis factor-alpha (TNF) promotes liver regeneration after partial hepatectomy (PH), the source of TNF is unknown. If Kupffer cells release TNF after PH, then Kupffer cell depletion by gadolinium chloride (GdCl) should inhibit liver regeneration. To test this hypothesis, cytokine expression and regenerative events were compared in GdCl-treated and control rats. Functional assays and Northern blot analysis of a Kupffer cell-specific mRNA confirmed that GdCl depleted Kupffer cells. Despite this, semiquantitative reverse transcription-polymerase chain reaction analysis of total hepatic RNA showed six- to eightfold higher levels of TNF transcripts in GdCl-treated rats. In this group, PH caused 12-to 16-fold greater induction of interleukin-6, a TNF-inducible cytokine, and two- to threefold greater induction of several cytokine-regulated genes (c-jun, C/EBP-beta, and C/EBP-delta). GdCl also amplified regeneration-associated increases in the DNA binding activity of AP-1, a growth regulatory transcription factor. Furthermore, hepatic incorporation of [3H]thymidine, expression of the S-phase antigen, proliferating cell nuclear antigen, and the hepatocyte mitotic index were each significantly greater in GdCl-treated rats. Thus, although GdCl causes Kupffer cell depletion, it does not decrease liver TNF and actually enhances liver regeneration after PH.

Animals↗
PubMed1996

Differential regulation of hepatocyte DNA synthesis by cAMP in vitro in vivo.

Adenosine 3',5'-cyclic monophosphate (cAMP) prevents epidermal growth factor (EGF)-induced DNA synthesis in many types of cultured cells, including hepatocytes, but its effects on cellular proliferation in vivo are unknown. This study compares the effects of supplemental cAMP on hepatocyte proliferation induced in vivo by 70% partial hepatectomy (PH) and in vitro by EGF and determines the effects of cAMP on AP-1, a family of growth-regulatory transcription factors, and the kinase cascades that normally activate AP-1. Although injection of dibutyryladenosine 3',5'-cyclic monophosphate (30 mg/kgip) at the time of PH increased liver cAMP concentrations at least 100-fold for several hours, it did not inhibit hepatic incorporation of [3H]thymidine or proliferating cell nuclear antigen expression 24 h after PH. cAMP treatment led to a complete inhibition of extracellular signal-related kinase (ERK) activity and transiently reduced NH2-terminal Jun nuclear kinase (JNK) activity after PH but did not decrease the expression of c-jun mRNA or protein. Consistent with the known cAMP stimulation of jun-B in cultured cells, cAMP treatment increased jun-B mRNA, protein, and DNA binding activity post-PH. Surprisingly, cAMP treatment enhanced Raf kinase activity after PH in rats. In primary hepatocyte cultures, supplemental cAMP inhibited JNK and ERK activity, total AP-1 and c-Jun transcriptional activities, and DNA synthesis. Thus elevated cAMP inhibited ERK and JNK activity in culture and in vivo and inhibited hepatocyte proliferation in culture but not in vivo. This suggests that in vivo mechanisms compensate for cAMP inhibition of certain growth-related signaling cascades and emphasizes potential risks of extrapolating from simple cell culture systems to explain physiology in intact animals.

Animals↗
PubMed1996

Ethanol exposure alters the phosphorylation of cyclic AMP responsive element binding protein and cyclic AMP responsive element binding activity in rat cerebellum.

The purpose of the present study was to track the acute effects of ethanol on the cerebellar adenylyl cyclase cascade from membrane to nucleus and to determine how this important signaling pathway neuroadapts during chronic ethanol exposure. An acute ethanol challenge increased cyclic AMP content and protein kinase A activity by 80% compared to control rats. In the nucleus the phosphorylated form of cAMP responsive element binding protein (CREB) increased 500%. Gel retardation assays with an oligomer encoding the rat proenkephalin cyclic AMP (CRE)1 were performed. Assays from protein derived from rats acutely exposed to ethanol identified three CRE-protein complexes also observed in assays of protein from saline-treated animals. However, after acute ethanol exposure, the intensity of the upper and middle CRE-protein complexes increased by 3-fold (280 +/- 10 vs. 70 +/- 3 arbitrary units; P < .01) compared to the sham treatment. Intensity of complex formation was still elevated 1 and 6 hr after ethanol exposure compared to sham conditions. In contrast, chronic ethanol treatment as well as pair-fed treatment did not alter the phosphorylation state of CREB or the intensity of the specific CRE-protein complexes on gel retardation assays. In summary, acute ethanol exposure resulted in the activation of the adenylyl cyclase signal transduction cascade from membrane to nucleus. In contrast, chronic ethanol exposure did not alter the phosphorylation of CREB or CRE binding activity. The behavioral significance of these events remain unclear, but may be related to the development of ethanol-induced tolerance in specific cerebellar functions.

Adenylyl Cyclases↗
PubMed1995

Tumor necrosis factor-alpha modulates CCAAT/enhancer binding proteins-DNA binding activities and promotes hepatocyte-specific gene expression during liver regeneration.

Injury-related cytokines, such as tumor necrosis factor-alpha (TNF), may preserve liver-specific gene expression during the subsequent regenerative response by modulating the activity of transcription factors, including CCAAT/enhancer binding proteins (C/EBPs), which regulate differentiated gene expression in hepatocytes. To test this theory, rats were treated with neutralizing antibody to TNF or nonimmune immunoglobulin before partial hepatectomy (PH) and regenerative changes in the messenger RNAs (mRNAs), proteins, and DNA-binding activities of C/EBP isoforms and the expression of a C/EBP-regulated gene, phosphoenol pyruvate carboxykinase (PEPCK), were compared. Before PH, the expressions of C/EBP-alpha, C/EBP-beta, and C/EBP-gamma were similar in the two treatment groups. Dimers containing C/EBP-alpha and C/EBP-beta accounted for virtually all of the C/EBP DNA binding activity and mRNA for PEPCK, the rate limiting hepatocyte enzyme for gluconeogenesis, was barely detected. After PH, in control rats, mRNA and nuclear protein concentrations of C/EBP-beta and C/EBP-gamma increased approximately fivefold by 3 hours after PH. This was accompanied by increased DNA binding activity of these C/EBP isoforms and decreased DNA binding activity of C/EBP-alpha. mRNA levels of PEPCK, a gene that is strongly transactivated by non-alpha C/EBP isoforms, increased fivefold. Pretreatment with anti-TNF antibodies prevented regenerative induction of C/EBP beta and gamma expression and DNA-binding activity. The nature of dimers binding to C/EBP cis-acting elements remained similar to that observed in liver before PH and increases in PEPCK mRNA were blunted. These results support the theory that TNF helps maintain liver-specific gene expression during liver regeneration by altering transcription factor complexes that regulate differentiated gene expression in hepatocytes.

Animals↗
PubMed1995

Vitamin E therapy of acute CCl4-induced hepatic injury in mice is associated with inhibition of nuclear factor kappa B binding.

Oxidative stress, with reactive oxygen intermediate formation, may represent a common mechanism by which liver injury is induced by diverse etiologies. Oxidative stress enhances nuclear factor kappa B (NF-kappa B) activity, and NF-kappa B activity has been shown to enhance the expression of cytotoxic cytokines. Acute hepatic injury caused by reactive oxygen intermediate production was induced by an intraperitoneal injection of CCl4 in mice. This injury was significantly inhibited by intravenous pretreatment of the mice with a water-soluble emulsion of alpha-tocopherol. Alpha-tocopherol treatment of the mice given the CCl4 also reduced the NF-kappa B binding to levels approaching those found in normal mice. In vitro treatment of a monocyte/macrophage cell line with CCl4 led to enhanced NF-kappa B binding and an increase in tumor necrosis factor-alpha (TNF-alpha) messenger RNA levels. Liver specimens taken from patients with acute fulminant hepatitis had markedly increased NF-kappa B binding activity in comparison with the binding of normal livers. These data demonstrate that abolishing acute hepatic injury with alpha-tocopherol, a free radical scavenger, also eliminated increased NF-kappa B binding. It is tempting to speculate that enhanced NF-kappa B expression caused by free radical production/oxidative stress may modulate liver injury, perhaps through an effect on cytotoxic cytokine synthesis.

Animals↗
PubMed1994

Selective induction of CCAAT/enhancer binding protein isoforms occurs during rat liver development.

BACKGROUND/AIMS: Recent evidence suggests that CCAAT/enhancer binding protein (C/EBP) transcription factors may regulate hepatocyte terminal differentiation. METHODS: To explore this possibility, the present study looked for variations in the expression or DNA binding activity of different C/EBP isoforms during rat postnatal liver development and determined which of the C/EBPs were expressed by adult hepatocytes in primary culture. RESULTS: In intact rats, hepatocyte proliferation is active for 2-3 weeks after birth. During this period of postnatal liver growth, several liver-specific functions emerge and C/EBP alpha, beta, and delta isoforms are induced. Nuclear expression of the 36-kilodalton C/EBP delta protein increases immediately after birth, followed first by increases in the 38-kilodalton C/EBP beta protein expression and then by increases in the 42-kilodalton C/EBP alpha protein expression. Changes in C/EBP DNA binding activity accompany developmental increases in C/EBP proteins. Messenger RNAs of all three C/EBP isoforms are expressed by mature hepatocytes in primary culture. CONCLUSIONS: Specific C/EBP isoforms are induced differentially during the course of rat postnatal liver development. Young adult rats and cultured adult hepatocytes express all three C/EBP isoforms. These results are consistent with (but do not prove) the theory that variations in C/EBP expression and function help regulate hepatocyte terminal differentiation.

Aging↗
PubMed1994

Altered levels of prothymosin immunoreactive peptide, a growth-related gene product, during liver regeneration after chronic ethanol feeding.

Liver regeneration is regulated by the orderly activation of growth-related genes. Although ethanol impairs induction of liver regeneration by partial hepatectomy, we have not identified ethanol-associated differences in the hepatic mRNA levels of several proto-oncogenes, including c-myc, which peaks 3-6 hr post-partial hepatectomy. Prothymosin alpha, a gene encoding a ubiquitous nuclear protein, is activated by c-myc in resting fibroblasts and has been implicated as a regulator of cell proliferation. Prothymosin alpha mRNA levels reportedly increase 12-32 hr post-partial hepatectomy, several hours after c-myc induction. We sought to determine if chronic ethanol intake alters the expected induction post-partial hepatectomy of prothymosin alpha steady-state mRNA expression and protein levels. Comparing rats chronically fed ethanol with pair-fed controls, we found no significant differences in steady-state levels of prothymosin alpha mRNA; however, we did see a delay in the increase of prothymosin immunoreactive peptide in rats chronically fed alcohol. This suggests that the inhibition in protein levels in ethanol fed rats is not due to lower steady-state mRNA levels, but may occur post-transcriptionally. Further data are needed to determine if this finding is important in the inhibition in cell growth following partial hepatectomy in rats chronically fed ethanol.

Alcoholism↗
PubMed1994

Tumor necrosis factor-alpha induces c-jun during the regenerative response to liver injury.

After liver injury, remaining hepatocytes proliferate to regenerate the liver. Although the precise mechanisms that initiate and localize regeneration are unknown, local induction of c-jun is a critical, early step in the response. Treatment of rats with antibodies to tumor necrosis factor-alpha (TNF-alpha), a mediator of liver injury, inhibits regenerative induction of jun nuclear kinase activity and nuclear c-jun expression and alters the DNA binding activity of the c-jun transcription factor, AP-1, in liver. Pretreatment with anti-TNF antibodies does not affect pulmonary or renal c-jun expression or AP-1 binding activity post-partial hepatectomy. In primary hepatocyte cultures, TNF-alpha directly promotes the proliferative actions of mitogens, supporting in vivo evidence that it sensitizes hepatocytes to mitogens. Thus local release of TNF may act in a paracrine fashion to initiate regeneration in the injured liver by promoting induction of critical growth-related genes, such as c-jun.

Animals↗
PubMed1994

Regenerative changes in C/EBP alpha and C/EBP beta expression modulate binding to the C/EBP site in the c-fos promoter.

CCAAT/enhancer binding proteins are a family of basic zipper DNA binding proteins that regulate transcription of several liver-specific genes and certain growth-related genes. Growth-related variations in the nuclear expression of one or more of the CCAAT/enhancer binding proteins may regulate the transition from the nonproliferative, differentiated phenotype of adult liver to the proliferative phenotype of regenerating liver. To evaluate this possibility, we used Northern- and Western-blot analyses to profile the expression of selected CCAAT/enhancer binding proteins in regenerating liver. Variations in CCAAT/enhancer binding protein expression were then correlated with changes in binding to the CCAAT/enhancer binding protein site of the c-fos promoter. Expression of both CCAAT/enhancer binding protein alpha and CCAAT/enhancer binding protein beta increases after partial hepatectomy. Steady-state levels of CCAAT/enhancer binding protein alpha mRNA increase 30% within an hour of partial hepatectomy (p < 0.05). This is followed by a transient increase in nuclear levels of CCAAT/enhancer binding protein alpha protein at 3 hr after partial hepatectomy (p = 0.08). In contrast, increases in CCAAT/enhancer binding protein beta mRNA and protein are more sustained. Levels of CCAAT/enhancer binding protein beta mRNA increase 400% to 500% within an hour of partial hepatectomy and remain increased throughout most of the prereplicative period (p < 0.01). Nuclear levels of CCAAT/enhancer binding protein beta protein are 200% to 300% greater than prehepatectomy levels at 3 hr (p < 0.001) to 6 hr (p < 0.05) and do not approach basal levels until 24 hr after partial hepatectomy. Gel mobility shift assays of nuclear extracts from regenerating livers indicate that these increases in nuclear protein expression are associated with increased DNA binding of CCAAT/enhancer binding protein alpha-beta heterodimers and beta-beta homodimers. These results demonstrate growth-related variations in the expression and DNA binding of both CCAAT/enhancer binding protein alpha and beta during liver regeneration and support the theory that altered CCAAT/enhancer binding protein DNA binding may contribute to regeneration-associated changes in liver cell phenotype.

Animals↗