Effects of Chronic Ethanol Administration on the Endocytosis of Cytokines by Rat Hepatocytes

Tuma, Dean J.; Todero, Sandra L.; Barak-Bernhagen, Mary A.; Sorrell, Michael F.

doi:10.1111/j.1530-0277.1996.tb01096.x

Cited by 15 publications

(7 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Calcium influx associated with electrical activity, transmembrane signaling (Kiss and Rougon, 1997), and intracellular and extracellular calcium levels have been suggested as regulating the mobilization of PSA‐NCAM to the cell surface (Kiss et al, 1994), and alcohol seems to modify calcium homeostasis affecting voltage‐ and receptor‐operated calcium channels (Catlin et al, 1998). In addition, alcohol seems to alter the endocytosis process in liver (Tuma et al, 1991, 1996) and in astrocytes (Megías et al., 2000), inducing an accumulation of glycoproteins in astroglial cells (Renau‐Piqueras et al, 1992; Vallés et al., 1994). These results suggest that alterations in the processes of exocytosis and endocytosis may be a general mechanism of ethanol toxicity in different cell types.…”

Section: Discussionmentioning

confidence: 99%

Alcohol Exposure Alters the Expression Pattern of Neural Cell Adhesion Molecules During Brain Development

Miñana¹,

Climent²,

Barettino³

et al. 2000

Journal of Neurochemistry

View full text Add to dashboard Cite

Neural cell adhesion molecules (NCAMs) play critical roles during development of the nervous system. The aim of this study is to investigate the possible effect of ethanol exposure on the pattern of expression and sialylation of NCAM isoforms during postnatal rat brain development because alterations in NCAM content and distribution have been associated with defects in cell migration, synapse formation, and memory consolidation, and deficits in these processes have been observed after in utero alcohol exposure. The expression of NCAM isoforms in the developing cerebral cortex of pups from control and alcohol-fed mothers was assessed by western blotting, ribonuclease protection assay, and immunocytochemistry. The highly sialylated form of NCAM [polysialic acid (PSA)-NCAM] is mainly expressed during the neonatal period and then is down-regulated in parallel with the appearance of NCAM 180 and NCAM 140. Ethanol exposure increases PSA-NCAM levels during the neonatal period, delays the loss of PSA-NCAM, decreases the amount of NCAM 180 and NCAM 140 isoforms, and reduces sialyltransferase activity during postnatal brain development. Neuraminidase treatment of ethanol-exposed neonatal brains leads to more intense band degradation products, suggesting a higher content of NCAM polypeptides carrying PSA in these samples. However, NCAM mRNA levels are not changed by ethanol. Immunocytochemical analysis demonstrates that ethanol triggers an increase in PSA-NCAM immunolabeling in the cytoplasm of astroglial cells, accompanied by a decrease in immunogold particles over the plasma membrane. These findings indicate that ethanol exposure during brain development alters the pattern of NCAM expression and suggest that modification of NCAM could affect neuronal-glial interactions that might contribute to the brain defects observed after in utero alcohol exposure. Key Words: Ethanol-Brain development-Neural cell adhesion molecules-Sialyltransferase-Astroglial cells. J. Neurochem. 75, 954 -964 (2000).

show abstract

Section: Discussionmentioning

confidence: 99%

Alcohol Exposure Alters the Expression Pattern of Neural Cell Adhesion Molecules During Brain Development

Miñana¹,

Climent²,

Barettino³

et al. 2000

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…The list so far includes: TGF-a, TNF-a, IL-6, EGF, and insulin (all in rat hepatocytes), growth hormone and insulin (in cirrhotic patients), and glucagon (in isolated rat liver plasma membranes) (Table 3) [10,18,62,63,71,91,99]. Remarkably, most of these molecules are known to be internalized by clathrinmediated endocytosis [8,9,23,61,73,80,88,103,105,109].…”

Section: Cytokines Growth Factors and Hormonesmentioning

confidence: 99%

Alcohol consumption impairs hepatic protein trafficking: mechanisms and consequences

2009

View full text Add to dashboard Cite

Alcoholic liver disease is a major biomedical health concern in the United States. Despite considerable research efforts aimed at understanding the progression of the disease, the specific mechanisms leading to alcohol-induced damage remain elusive. Numerous proteins are known to have alcohol-induced alterations in their dynamics. Defining these defects in protein trafficking is an active area of research. In general, two trafficking pathways are affected: transport of newly synthesized secretory or membrane glycoproteins from the Golgi to the basolateral membrane and clathrin-mediated endocytosis from the sinusoidal surface. Both impaired secretion and internalization require ethanol metabolism and are likely mediated by acetaldehyde. Although the mechanisms by which ethanol exposure impairs protein trafficking are not fully understood, recent work implicates alcohol-induced modifications on tubulin or components of the clathrin machinery as potential mediators. Furthermore, the physiological ramifications of impaired protein trafficking are not fully understood. In this review, we will list and discuss the proteins whose trafficking patterns are known to be impaired by ethanol exposure. We will then describe what is known about the possible mechanisms leading to impaired protein trafficking and how disrupted protein trafficking alters liver function and may explain clinical features of the alcoholic patient.

show abstract

“…Serum IL-6 levels were signi®cantly elevated in chronic ethanol feeding mice as demonstrated in Figure 1, however, the underlying mechanism is not clear. Impaired hepatocyte endocytosis of IL-6 (Tuma et al, 1996) during chronic ethanol consumption and elevated endotoxin that stimulates IL-6 expression (Panesar et al, 1999) could be mechanisms responsible for elevation of serum IL-6 levels. In contrast, acute exposure of primary hepatocytes to ethanol decreased the IL-6 secretion, which is probable due to an increase of IL-6 uptake after acute ethanol exposure (Deaciuc et al, 1996).…”

Section: Il-6 Plays An Important Role In Protection Of Ethanol-inducementioning

confidence: 99%

Elevated interleukin-6 during ethanol consumption acts as a potential endogenous protective cytokine against ethanol-induced apoptosis in the liver: involvement of induction of Bcl-2 and Bcl-xL proteins

et al. 2002

View full text Add to dashboard Cite

Elevation of serum interleukin-6 (IL-6) levels is always associated with alcoholic liver disease (ALD), but the significance of such elevation is not clear. Here we show that chronic ethanol consumption induces significant apoptosis in the liver of IL-6 (-/-) mice but not IL-6 (+/+) mice. IL-6 (-/-) hepatocytes are more susceptible to ethanol- and tumor necrosis factor alpha- (TNFalpha-) induced apoptotic killing, which can be corrected by IL-6. Expression of both anti-apoptotic (such as Bcl-2 and Bcl-x(L)) and proapoptotic (such as Bax) proteins is markedly elevated in the liver of human ALD and chronically ethanol-fed IL-6 (+/+) mice. On the contrary, induction of Bcl-2 and Bcl-x(L) is not observed in the liver of chronically ethanol-fed IL-6 (-/-) mice, whereas expression of Bax protein remains elevated. Injection of IL-6 markedly induces expression of Bcl-2 and Bcl-x(L) but not Bax in the liver. Finally, high concentrations of ethanol inhibit IL-6-activated anti-apoptotic signal, but increasing the concentrations of IL-6 is able to overcome such inhibitory effect. These findings suggest that elevated serum IL-6 levels in ALD may overcome the inhibitory effect of ethanol on IL-6-mediated anti-apoptotic signals and prevent alcohol-induced hepatic apoptosis by induction of Bcl-2 and Bcl-x(L).

show abstract

Effects of Chronic Ethanol Administration on the Endocytosis of Cytokines by Rat Hepatocytes

Cited by 15 publications

References 34 publications

Alcohol Exposure Alters the Expression Pattern of Neural Cell Adhesion Molecules During Brain Development

Alcohol Exposure Alters the Expression Pattern of Neural Cell Adhesion Molecules During Brain Development

Alcohol consumption impairs hepatic protein trafficking: mechanisms and consequences

Elevated interleukin-6 during ethanol consumption acts as a potential endogenous protective cytokine against ethanol-induced apoptosis in the liver: involvement of induction of Bcl-2 and Bcl-xL proteins

Contact Info

Product

Resources

About