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J B Hoek

Publications and source records attributed to J B Hoek.

At least 55 records · Page 3Linked to original sources
PubMed1995

Calcium ion-dependent signalling and mitochondrial dysfunction: mitochondrial calcium uptake during hormonal stimulation in intact liver cells and its implication for the mitochondrial permeability transition.

Hormones that elevate cytosolic Ca2+ concentrations ([Ca2+]cyt) often use Ca2+ as a messenger to activate intramitochondrial metabolic processes. However, the mitochondrial Ca2+ level also regulates the activation of the mitochondrial permeability transition (MPT), a process that involves the assembly of a high conductance proteinaceous pore across the inner and outer membrane. Studies on intact liver cells indicate that the MPT is a critical step in the cell killing induced by anoxia or respiratory inhibitors. In this study, we used freshly isolated hepatocytes to investigate to what extent the elevation of [Ca2+]cyt by vasopressin or other agonists causes Ca2+ accumulation in the mitochondria and how this treatment affects the mitochondrial susceptibility to undergo the MPT. Hepatocytes were incubated with vasopressin, glucagon, or with thapsigargin (an inhibitor of the endoplasmic reticulum Ca2+ pump) prior to permeabilization with digitonin. Mitochondrial Ca2+ accumulation was determined by following the ionomycin-induced Ca2+ release in permeabilized cells and mitochondrial swelling was studied by following cyclosporin A-sensitive light scattering changes induced by phenyl-arsenoxide and rotenone. The results indicate that agents that elevate [Ca2+]cyt cause a significant Ca2+ accumulation in the mitochondria. Excessive Ca2+ accumulation (> 10-fold increase over basal levels) was obtained with the combination of vasopressin and glucagon or with incubations containing thapsigargin. These conditions were also associated with a marked increase in rotenone-induced mitochondrial swelling. However, the more modest increase in mitochondrial Ca2+ content after treating cells with vasopressin alone did not enhance the swelling response; instead, vasopressin suppressed mitochondrial swelling compared to control incubations. Vasopressin also partly suppressed the swelling associated with thapsigargin treatment, although it did not significantly affect the Ca2+ accumulation under these conditions. This effect of vasopressin was mimicked by phorbol ester, suggesting a role for protein kinase C. The data indicate that mitochondrial Ca2+ accumulation following elevation of elevation of [Ca2+]cyt enhances the susceptibility for activation of the MPT, a response that may increase cell injury during anoxia or in response to other challenges. However, hormones also activate protective responses in the cell that suppress the MPT.

Animals↗
PubMed1995

Ca2+ depletion prevents anoxic death of hepatocytes by inhibiting mitochondrial permeability transition.

Removal of Ca2+ from the culture medium or treatment with the intracellular Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N', N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM) prevented the killing of rat hepatocytes by anoxia and rotenone, but not by cyanide. Neither manipulation prevented the loss of the mitochondrial membrane potential or the depletion of ATP. A mitochondrial permeability transition (MPT) was demonstrated in digitonin-permeabilized hepatocytes as an increased [3H]sucrose-accessible space sensitive to cyclosporin A (CyA). Ca2+ depletion by either means prevented the MPT measured in intact cells made anoxic or treated with rotenone. In isolated mitochondria deenergized by rotenone, BAPTA-AM prevented the MPT induced by palmitoyl CoA. By contrast, in isolated mitochondria deenergized by cyanide, BAPTA-AM alone did not prevent the MPT. Rather, BAPTA-AM plus CyA were required. Similarly, the killing of cultured hepatocytes by cyanide was prevented by BAPTA-AM plus CyA, but not by either agent alone. The MPT in intact cells treated with cyanide was also prevented by BAPTA-AM plus CyA. These data define a specific requirement for Ca2+ in the killing of hepatocytes that follows the inhibition of electron transport. A model is presented in which the MPT depends on factors that modulate the sensitivity of the permeability transition to the matrix concentration of Ca2+.

Adenosine Triphosphate↗
PubMed1994

Protoporphyrin IX, an endogenous ligand of the peripheral benzodiazepine receptor, potentiates induction of the mitochondrial permeability transition and the killing of cultured hepatocytes by rotenone.

The peripheral benzodiazepine receptor (PBzR) is associated with the outer mitochondrial membrane. Protoporphyrin IX (PPIX), an endogenous substance with high affinity for the PBzR, induced the inner membrane permeability transition (MPT) in respiring liver mitochondria de-energized by carbonyl cyanide p-trifluoromethoxyphenylhydrazone. Cyclosporin A (CyA), an inhibitor of the permeability transition, prevented this effect. In cultured hepatocytes, the MPT was measured as an increased [3H]sucrose-accessible space sensitive to CyA. Nanomolar concentrations of PPIX potentiated the induction of the MPT and the extent of cell killing in hepatocyte cultures de-energized by rotenone. CyA prevented the enhanced cell killing by PPIX. PPIX did not increase the rate or extent of ATP depletion, the loss of the mitochondrial membrane potential, or the accumulation of long chain acyl-CoA thioesters. The association of the PBzR with the voltage-dependent anion channel of the outer mitochondrial membrane and with the adenine nucleotide carrier of the inner membrane suggests that this complex mediates the transport of PPIX across the mitochondrial membranes. In turn, this same complex participates in the MPT. Thus, the same structural complex (PBzR, voltage-dependent anion channel, and adenine nucleotide carrier) can interact with the endogenous substrate PPIX to result in different functional consequences depending on the state of mitochondrial energization.

Adenosine Triphosphate↗
PubMed1994

Leupeptin inhibits phospholipases D and C activation in rat hepatocytes.

The relationship between phospholipase D and C activation was studied in intact rat hepatocytes and rat liver plasma membranes. In intact hepatocytes, in the presence of ethanol, vasopressin, phorbol ester, and calcium independently stimulated phosphatidylethanol (PETH) formation, a specific marker of phospholipase D activity. Leupeptin (10-1500 microM) inhibited PETH formation induced by vasopressin, but was ineffective in response to phorbol ester or calcium. Leupeptin also inhibited the formation of inositol phosphates in intact cells in response to vasopressin. In liver plasma membranes, GTP[S] induced the production of phosphatidic acid and, in the presence of ethanol, PETH. Plasma membrane-associated phospholipase D did not require calcium and was insensitive to protein kinase C inhibitors. Leupeptin inhibited PETH formation in response to GTP[S]. The inhibition by leupeptin could be overcome by increasing the concentration of GTP[S]. In plasma membranes, the inhibitory effects of leupeptin on phospholipase D occurred at doses that far exceed those required to maximally inhibit proteolysis. These data highlight a central role for phospholipase C in the activation of phospholipase D, and a minor role for a direct G-protein activation. The findings also demonstrate a novel use of leupeptin as an inhibitor of phospholipases D and C, perhaps at the level of a G protein.

Animals↗
PubMed1994

Activation and desensitization of phospholipase D in intact rat hepatocytes.

Activation of phospholipase D (PLD) by receptor-coupled stimuli (vasopressin, ATP), phorbol esters, and Ca2+ ionophores was studied in isolated rat hepatocytes, double labeled with [3H]arachidonate and [14C]stearate. Phosphatidylethanol (Peth) was formed when cells were stimulated in the presence of ethanol. The effect of combinations of agonists was not additive, indicating that the same PLD isozyme(s) were activated. With all agonists, the 3H- and 14C-specific radioactivity in Peth was higher than in any of the main phospholipid classes. The 3H/14C ratios of Peth and phosphatidylcholine (PC) were identical and differed from other phospholipid classes, indicating that the predominant PLD substrate was a PC pool labeled preferentially with radioactive fatty acids. Ethanol (50-300 mM) decreased the initial rate of phosphatidic acid (PA) formation, but did not affect total PLD activity. Agonist-induced changes in steady state accumulation of PA or 1,2-diacylglycerol were also unaffected. A slow degradation of Peth (apparent t1/2 > 60 min) occurred after ethanol removal from cells prestimulated with vasopressin. The rate of degradation was unaffected by agonists that stimulate PLD. Thus, Peth formation is a suitable cumulative indicator for PLD activation in intact hepatocytes. Peth accumulation declined over a period of 5-20 min, depending on the agonist. The decline was not due to increased Peth degradation, or limitations in substrate supply to PLD, or enzyme inhibition by accumulated Peth. Instead, a homologous desensitization of PLD occurs with all agonists. This desensitization may involve the action of selective protein kinase C isozymes.

Adenosine Triphosphate↗
PubMed1994

The role of cytosolic Ca2+, protein kinase C, and protein kinase A in hormonal stimulation of phospholipase D in rat hepatocytes.

Ca(2+)-dependent and protein kinase C-dependent mechanisms of phospholipase D (PLD) activation were studied in rat hepatocytes by measuring phosphatidylethanol (Peth) formation in the presence of ethanol. Stimulation of Peth formation by 12-O-tetradecanoyl-phorbol 13-acetate (TPA), vasopressin, or A23187 was inhibited by multiple protein kinase C inhibitors or by protein kinase C down-regulation, indicating that this enzyme is involved in the action of all these agents. A controlled elevation of the cytosolic Ca2+ concentration ([Ca2+]cyt) over the range of 0.1-2.0 microM activated Peth formation in the absence of other agonists. Staurosporin potentiated Ca(2+)-induced Peth formation by shifting the [Ca2+]cyt dose-response curve to the left. Other protein kinase C inhibitors (calphostin C, bisindolylmaleimide) inhibited Ca(2+)-mediated Peth formation, but this inhibition was reduced in staurosporin-treated cells. Okadaic acid potentiated PLD activation by TPA, but suppressed PLD activation by elevated [Ca2+]cyt. Desensitization of TPA-induced PLD activity did not affect PLD activation by Ca2+. These data indicate that [Ca2+]cyt and protein kinase C control distinct pathways of PLD activation, but the Ca(2+)-mediated pathway is suppressed by a staurosporin-sensitive protein kinase. Both mechanisms contribute to vasopressin-induced Peth formation in intact hepatocytes. Activation of protein kinase A enhanced vasopressin-induced Peth formation, but not TPA-stimulated or Ca(2+)-stimulated stimulated Peth formation. Protein kinase A acted by enhancing hormonal Ca2+ mobilization, rather than by directly activating PLD, and thereby shifted the balance of Ca(2+)-dependent and protein kinase C-dependent activation mechanisms of PLD in intact cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1994

Inhibition of ethanol-induced inositol phosphate formation and Ca(2+) mobilization by okadaic acid in rat hepatocytes: evidence for a role of protein phosphatases in the modulation of phospholipase C by ethanol.

The effect of the protein phosphatase inhibitor okadaic acid on phospholipase C (PLC)-linked signal transduction processes was investigated in intact hepatocytes. A short (5 min) pretreatment of the hepatocytes with okadaic acid (1 mu M) markedly inhibited a subsequent stimulation of PLC by ethanol as well as by receptor-mediated stimuli (vasopressin and phenylephrine). Okadaic acid inhibited the agonist-induced hydrolysis of polyphosphoinositides, the accumulation of inositol trisphosphate (InsP(3)) and the increase in cytosolic Ca(2+) concentrations. The inhibition could be overcome by high concentrations of vasopressin or ethanol, but only partly so with phenylephrine. A comparison of the sensitivity of different agonists at similar rates of InsP(3) accumulation and Ca(2+) mobilization indicated that ethanol-induced PLC activation was more resistant to the effects of okadaic acid than the hormonal agonists. Moreover, the stimulation of PtdInsP kinase by ethanol, which accompanies PLC activation, was refractory to okadaic acid treatment. These findings suggest that receptor-mediated PLC activation is subject to multiple controls by phosphorylation-dephosphorylation, not all of which affect the actions of ethanol on this signal transduction system.

Animals↗
PubMed1993

Stimulation of protein synthesis in isolated pancreatic acini from chronically ethanol-fed rats is due to alterations in post-transcriptional regulation.

In an earlier study, we reported that isolation of acini from the pancreas of rats fed ethanol chronically, led to a 2- to 3-fold increase in the rate of protein synthesis compared to acini from rats fed the control diet. In the present study, we wanted to investigate whether the enhanced rate of protein synthesis was due to an increased rate of degranulation, reflecting a stimulation of cellular signal transduction processes, and/or to changes at the level of transcription/translation. The rate of degranulation was monitored by initially prelabelling the secretory proteins in vivo with [3H]leucine followed by determination of their fate in the intact tissue as well as in the subsequently isolated acini. The recovery of the label in isolated acini as a fraction of that incorporated into the tissue was similar for control and ethanol-fed groups, suggesting that ethanol feeding had no effect on the rate of degranulation during the isolation of acini. The rate of incorporation of [3H]uridine into total RNA was about 70% higher in acini from the ethanol-fed group as compared to the control group, suggesting a higher rate of transcription. However, the steady-state level of mRNA for trypsinogen, a representative digestive enzyme mRNA, showed only a moderate increase of 20% in acini from the ethanol-fed group compared to those from the intact tissue. These results suggest that the increased rate of protein synthesis in isolated acini from ethanol-fed rat pancreas is primarily due to post-transcriptional modifications.

Animals↗
PubMed1993

Multiple mechanisms by which protein kinase A potentiates inositol 1,4,5-trisphosphate-induced Ca2+ mobilization in permeabilized hepatocytes.

The mobilization of Ca2+ from intracellular stores by Ins(1,4,5)P3 in suspensions of permeabilized rat hepatocytes was potentiated by preincubating intact cells with adenosine 3':5'-cyclic phosphorothioate (cpt-cAMP), or by addition of the catalytic subunit of cyclic-AMP-dependent protein kinase (PKA) after cell permeabilization. This action of PKA involved both an enhancement in Ins(1,4,5)P3 sensitivity and an increase in the size of the Ins(1,4,5)P3-releasable Ca2+ pool. Inclusion of the protein phosphatase inhibitor okadaic acid in the permeabilization medium augmented the effects of PKA. Treatment with PKA catalytic subunit also increased the rate of ATP-dependent Ca2+ sequestration. To determine whether the effects of PKA on the Ca(2+)-release mechanism were secondary to alterations in the Ca2+ load of the Ins(1,4,5)P3-sensitive stores, a method was developed using Mn2+ as a Ca2+ surrogate to examine the permeability properties of the Ins(1,4,5)P3-gated channels independent of Ca2+ fluxes. This approach utilized the ability of Mn2+ to quench the fluorescence of fura-2 compartmentalized within intracellular Ca2+ stores in an Ins(1,4,5)P3-dependent manner, with thapsigargin added to block the ATP-activated Ca2+ pump and to ensure that the Ca2+ stores were fully depleted of Ca2+. The initial rate and extent of Mn2+ quenching of compartmentalized fura-2 was increased in a dose-dependent manner by Ins(1,4,5)P3. PKA activation increased both the initial rate and the extent of Mn2+ quenching at sub-maximal Ins(1,4,5)P3 doses, but there was no effect on the quench rate in the presence of saturating Ins(1,4,5)P3. However, the amount of compartmentalized fura-2 that could be quenched by Mn2+ in the presence of maximal Ins(1,4,5)P3 was increased by PKA. These data suggest two distinct actions of PKA on the Ins(1,4,5)P3-sensitive Ca2+ stores. (1) Modification of the ion-permeability properties of the Ins(1,4,5)P3 receptor/channel through an increase in the sensitivity to Ins(1,4,5)P3 for channel opening. (2) A recruitment of Ca2+ stores from the Ins(1,4,5)P3-insensitive pool. Both actions were independent of the Ca(2+)-loading state of the stores. Imaging studies of single permeabilized hepatocytes showed that the Ins(1,4,5)P3-sensitive stores were distributed throughout the cell and PKA enhanced the rate of Ins(1,4,5)P3-stimulated Mn2+ quench in individual cells, without modifying the subcellular distribution of Ins(1,4,5)P3-sensitive stores.

Animals↗
PubMed1993

Cyclosporin and carnitine prevent the anoxic death of cultured hepatocytes by inhibiting the mitochondrial permeability transition.

Cyclosporin A (CyA) and L-carnitine (LC) prevented the killing of cultured hepatocytes by anoxia and rotenone but not by cyanide. Neither CyA nor LC affected the rate or extent of the loss of the mitochondrial membrane potential or the rate or extent of the depletion of ATP. Atractyloside blocked the ability of both CyA and LC to protect, and D-carnitine antagonized the effect of LC but not that of CyA. Cell killing by cyanide was prevented when the phospholipase A2 inhibitor butacaine was added together with CyA. Butacaine by itself had no effect on cell killing. In a swelling assay with isolated rat liver mitochondria having a low calcium content, phenylarsine oxide or palmitoyl-CoA induced the inner membrane permeability transition when electron transport was inhibited by rotenone or cyanide. CyA prevented the permeability transition with rotenone but not with cyanide, and atractyloside reversed the effect of CyA. LC prevented the permeability transition occurring with palmitoyl-CoA plus rotenone but not with palmitoyl-CoA plus cyanide. Atractyloside and D-carnitine antagonized the protective effect of LC. Inhibition of the cyanide-dependent permeability transition in isolated liver mitochondria required the presence of both CyA and butacaine. These data document the close correlation between the effect of CyA and LC on the response of cultured hepatocytes to inhibition of mitochondrial electron transport and their ability to prevent the permeability transition in isolated mitochondria. It is concluded that the ability of CyA and LC to protect cultured hepatocytes is a consequence of their ability to prevent the mitochondrial permeability transition, indicating that this event is likely to be causally linked to the genesis of irreversible injury. Thus, cell death with anoxia or inhibitors of electron transport is related to a mitochondrial alteration by a mechanism that is independent of the maintenance of a membrane potential or cellular stores of ATP.

4-Aminobenzoic Acid↗
PubMed1993

Unilateral nephrectomy selectively stimulates phospholipase D in the remaining kidney.

The activation of phospholipase D in the kidney could be detected in vivo in rats treated with ethanol by the accumulation of phosphatidylethanol. Unilateral nephrectomy stimulated the activity of phospholipase D in the remaining kidney as indicated by an increase in the level of phosphatidylethanol. A significant increase in phosphatidylethanol level was observed as early as 5 min after contralateral nephrectomy and peak accumulation (200% of control) was observed after 15 min. The phosphatidylethanol level decreased again to the basal level after 2 h. The accumulation of phosphatidylethanol was specific for kidney and the product was localized primarily in the cortex. Phospholipase D activity in kidney cortical slices from untreated rats was stimulated in vitro by plasma obtained from unilaterally nephrectomized rats, indicating that circulating factors in the plasma are responsible for the activation of phospholipase D. The phospholipase D activation by plasma from uninephrectomized animals was selectively inhibited by the tyrosine kinase inhibitor genistein, but not by the protein kinase C inhibitor H7. It is concluded that phospholipase D activity is stimulated as an early signal transduction event in compensatory kidney growth.

Alcoholic Intoxication↗
PubMed1993

ATP synthase activity is required for fructose to protect cultured hepatocytes from the toxicity of cyanide.

The contributions of the loss of the mitochondrial membrane potential (MMP) and a depletion of ATP to the genesis of lethal injury were evaluated in the killing of cultured hepatocytes by cyanide (CN). The glycolytic production of ATP from fructose (Fru) maintained the MMP and prevented the killing by CN. Inhibition of the mitochondrial ATP synthase by 0.1 micrograms/ml oligomycin (Oligo) reduced ATP stores at the same rate and to the same extent as did 1 mM CN. With Oligo there was no loss of the MMP, and the hepatocytes maintained viability over the 6 h during which CN killed all of the cells. Oligo had no effect on the rate of killing by CN. However, Oligo reversed the protective effect of Fru on CN-induced killing, a result that correlated with the loss of MMP but not with the depletion of ATP. Neither Fru nor Oligo affected the intracellular acidosis achieved with CN alone. Fru also prevented toxicity of the uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP), a result that correlated with the preservation of MMP. Oligo potentiated the toxicity of CCCP. It is concluded that a functioning mitochondrial ATP synthase is required for the production of ATP from Fru to prevent the killing of hepatocytes by CN. The extent of killing correlated closely with changes in the MMP but not with changes in the content of ATP.

Adenosine Triphosphate↗
PubMed1993

Mitochondrial respiratory chain activity in skeletal muscle from patients with Parkinson's disease.

Different abnormalities in mitochondrial electron transport chain activity have been demonstrated in muscle and other tissues of patients with idiopathic Parkinson's disease (PD). We studied eight Spanish patients with PD to evaluate the functional activity of the electron transport chain in muscle mitochondria from patients of this country. We found lower complex I activity (nmol.min-1.mg-1) in patients (245.8 +/- 42.8) than in controls (331.6 +/- 60.1) (p = 0.004) and lower complex IV activity in patients (46.1 +/- 9) than in controls (144.1 +/- 42.3) (p = 0.00001). Complex V activity was also decreased in two patients and complex II and III activities were normal in all of them. Although these results strongly suggest an alteration in mitochondrial DNA in PD, the various electron transport chain defects in different tissues seem to be nonspecific.

Aged↗
PubMed1992

The role of the matrix calcium level in the enhancement of mitochondrial pyruvate carboxylation by glucagon pretreatment.

The effect of Ca2+ on the rate of pyruvate carboxylation was studied in liver mitochondria from control and glucagon-treated rats, prepared under conditions that maintain low Ca2+ levels (1-3 nmol/mg of protein). When the matrix-free [Ca2+] was low (less than 100 nM), the rate of pyruvate carboxylation was not significantly different in mitochondria from control and glucagon-treated rats. Accumulation of 5-8 nmol of Ca2+/mg, which increased the matrix [Ca2+] to 2-5 microM in both preparations, significantly enhanced pyruvate carboxylase flux by 20-30% in the mitochondria from glucagon-treated rats, but had little effect in control preparations. Higher levels of Ca2+ (up to 75 nmol/mg) inhibited pyruvate carboxylation in both preparations, but the difference between the mitochondria from control and glucagon-treated animals was maintained. The enhancement of pyruvate dehydrogenase flux by mitochondrial Ca2+ uptake was also significantly greater in mitochondria from glucagon-treated rats. These differential effects of Ca2+ uptake on enzyme fluxes did not correlate with changes in the mitochondrial ATP/ADP ratio, the pyrophosphate level, or the matrix volume. Arsenite completely prevented 14CO2 incorporation when pyruvate was the only substrate, but caused only partial inhibition when succinate and acetyl carnitine were present as alternative sources of energy and acetyl-CoA. Under these conditions, mitochondria from glucagon-treated rats were less sensitive to arsenite than the control preparations, even at low Ca2+ levels. We conclude that the Ca(2+)-dependent enhancement of pyruvate carboxylation in mitochondria from glucagon-treated rats is a secondary consequence of pyruvate dehydrogenase activation; glucagon treatment is suggested to affect the conditions in the mitochondria that change the sensitivity of the pyruvate dehydrogenase complex to dephosphorylation by the Ca(2+)-sensitive pyruvate dehydrogenase phosphatase.

Adenosine Diphosphate↗
PubMed1992

Oxidative metabolism in muscle mitochondria from patients with chronic alcoholism.

We investigated the effect of long-term ethanol intake on the function of skeletal muscle mitochondria from 30 human alcoholics. Mitochondrial studies included (1) oxidative phosphorylation, (2) the activity of the individual complexes of the respiratory chain, and (3) the cytochrome content. State 3 and state 4 oxidation rates with glutamate-malate, succinate, tetramethyl-p-phenylenediamine-ascorbate, and acetylcarnitine-malate, the activity of the individual complexes of the respiratory chain, and the concentration of mitochondrial cytochromes were comparable in control subjects and alcoholic patients, and also in myopathic and nonmyopathic alcoholic patients. These results demonstrate that alcoholic myopathy is not associated with a deficiency in mitochondrial energy supply.

Adult↗
PubMed1992

Hepatic fibrosis in rats produced by carbon tetrachloride and dimethylnitrosamine: observations suggesting immunoassays of serum for the 7S fragment of type IV collagen are a more sensitive index of liver damage than immunoassays for the NH2-terminal propeptide of type III procollagen.

Liver fibrosis was induced in rats both with carbon tetrachloride and dimethylnitrosamine. Assays were performed on steady-state levels of messenger RNAs in the liver for several collagens and basement membrane components. The results indicated marked increases in the steady-state levels of messenger RNA for type I collagen, type III collagen, type IV collagen and the B2 component of laminin. In the same animals, immunoassays were performed for serum levels of the N-terminal propeptide of type III procollagen and the 7S fragment of type IV collagen. The results demonstrated an increase in the serum levels of 7S fragment that occurred early and closely paralleled the increase in the steady-state levels of messenger RNA for the alpha 1(IV) chain of type IV collagen. In contrast, no significant increase was seen in the serum levels of the N-propeptide of type III procollagen. The results suggest that immunoassays for 7S fragment of type IV collagen in serum are a more sensitive index for liver cell damage and fibrosis than assays for the N-propeptide of type III procollagen. The results suggest that greater attention should be paid to assays of 7S fragments in assessing hepatic fibrosis in man.

Animals↗
PubMed1992

Ethanol and signal transduction in the liver.

The liver is a major target for both short- and long-term actions of ethanol. The mechanisms that mediate the response of cells and tissues to chronic intake of ethanol are unknown, but it is likely that both adaptive and deleterious responses are triggered by short-term interactions of the cell with ethanol. Cellular signaling processes are candidates to mediate the connection between short- and long-term actions of ethanol. Receptor-coupled signal transduction systems in the plasma membrane of many different cell types are affected by ethanol. In the liver, the signaling processes associated with phospholipases C and D are particularly responsive to ethanol. In this review, we investigate the direct and indirect short-term effects of ethanol on the signal transduction systems in liver and discuss the possible implications for the responses of the liver to chronic ethanol exposure.

Adaptation, Physiological↗