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1.
Dr. Jacques F. G. M. Meis P. Jos M. Rijntjes Jan Peter Verhave Thivi Ponnudurai Michael R. Hollingdale Judith E. Smith Robert E. Sinden Paul H. K. Jap Joseph H. E. T H Meuwissen Sing Hiem Yap 《Cell and tissue research》1986,244(2):345-350
Summary Recent advances in the ability to culture the hepatic forms of mammalian malaria parasites, particularly of the important human pathogen Plasmodium falciparum have provided novel opportunities to study the ultrastrucural organisation of the parasite in its natural host cell the human hepatocyte. In this electron-microscopic and immunofluorescence study we have found the morphology of both parasite and host cell to be well preserved. The exoerythrocytic forms, which may be found at densities of up to 100/cm2, grow at rates comparable to that in vivo in the chimpanzee. In the multiplying 5- and 7-day schizogonic forms the ultrastructural organisation of the parasite bears striking resemblances to other mammalian parasites, e.g., the secretory activity and distribution of the peripheral vacuole system, but also homology with avian parasites, e.g., in nuclear and nucleolar structure and mitochondrial form. The latter homologies support earlier suggestions of the close phylogenetic relationship of P. falciparum with the avian parasites. Evidence is also presented showing the persistence of the cytoskeleton of the invasive sporozoite within the cytoplasm of the ensuing rapidly growing vegetative parasites. 相似文献
2.
Laurence Bianchini Barthélémy Fossat Jacqueline Porthé-Nibelle Brahim Lahlou 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》1990,160(1):93-98
Summary Na+, K+ exchanges were studied in isolated hepatocytes of the rainbow trout, Salmo gairdneri. Ouabain at 10–4
M produced maximal inhibition (95%) of K+ uptake and enhanced intracellular Na+ accumulation, showing that active fluxes account for a very large proportion of Na+ and K+ exchanges. Inhibition of the Na–K pump by ouabain was significant at low concentrations (10–8
M). When external K+ concentration was reduced from 7 mM to 0.5 mM, half maximum inhibition (IC50) of K+ uptake was obtained at a 22-fold lower concentration of ouabain confirming that ouabain and potassium compete at the same pump site. Time-course analysis of [3H]ouabain binding indicated a two-component kinetics: one component saturable and dependent on K+ concentration in the medium, the other linear and independent of external K+. The ouabain binding site number, determined by Scatchard plots, remained constant (ca. 2.5·105 per cell) and independent of the external K+ concentration (7, 0.5 or 0 mM), while the dissociation constant (KD) decreased from 4.2 M to 7.3 nM when K+ was removed from the Hank's medium. These ouabain binding sites are characterized by an exceptionally low turnover rate (400 min–1), as estimated from ouabain-sensitive K+ flux, in comparison to those described in other cell types of higher vertebrates. At each external K+ concentration studied, the inhibition of K+ uptake and ouabain binding measured as a function of ouabain concentration indicated a strict correlation between the degree of K pump inhibition and the amount of bound glycoside. 相似文献
3.
4.
Nobuyoshi Shiojiri 《Cell and tissue research》1994,278(1):117-123
The differentiation of hepatocytes and biliary epithelial cells has been histochemically analyzed with anti-calf cytokeratin antiserum in the fetal mouse liver. Almost all young fetal hepatocytes transiently express bile-duct-specific cytokeratin; subsequently, the strong staining of the cytokeratin is confined to progenitor cells of intrahepatic biliary epithelial cells around portal veins. These results suggest that all fetal hepatocytes are bi-potent in terms of the differentiation of mature hepatocytes and intrahepatic bile-duct cells, and that the microenvironment around portal veins plays an important role in bile-duct differentiation. Large periportal hepatocytes continue to stain weakly for cytokeratin until 2 weeks after birth, although the number of positive hepatocytes decreases with development. The differentiation of bile ducts from periportal hepatocytes may continue for 2 weeks after birth. 相似文献
5.
Lentiviral vectors have been used for gene transfer into the liver but their ability to efficiently transduce quiescent hepatocytes
remains controversial. Lentivirus-mediated gene transfer is more efficient in cycling cells. We determine the effect of H-IL6
in the lentiviral transduction. The lentiviral vector was used to transduce HepG2 cells and mice liver cells, previously treated
with H-IL6. The highest transduction level was observed in HepG2 cells treated with 30 ng/mL H-IL6 and in the mice that received
4 μg H-IL6. Our results suggest that H-IL6 is an inducer of lentiviral gene transfer into the liver cells without any toxicity. 相似文献
6.
In order to achieve the goal of developing extracorporeal liver support devices, it is necessary to optimise bioprocess environment
such that viability and function are maximised. Optimising culture medium composition and controlling the constitution of
the cellular microenvironment within the bioreactor have for many years been considered vital to achieving these aims. Coupled
to this is the need to understand apoptosis, the prime suspect in the demise of animal cultures, including those of hepatocytes.
Results presented here show that absent nutrients including glucose and amino acids play a substantial part in the induction
of apoptosis. The use of chemical apoptosis inhibitors was utilised to investigate key components of hepatic apoptosis where
caspases, predominantly caspase 8, were implicated in staurosporine (STS)-induced HepZ apoptosis. Caspase 9 and 3 activation
although recorded was of less significance. Interestingly, these results were not consistent with those of mitochondrial membrane
depolarisation where inhibition of caspase activation appeared to drive depolarisation. Inhibition of mitochondrial permeability
transition and use of anti-oxidants was unsuccessful in reducing apoptosis, caspase activation and mitochondrial membrane
depolarisation. In further studies, the anti-apoptotic gene bcl-2 was over-expressed in HepZ, resulting in a cell line that was more robust and resistant to death induced by glucose and cystine
deprivation and treatment with STS. Bcl-2 did not however show significant cytoprotectivity where apoptosis was stimulated
by deprivation of glutamine and serum. Overall, results indicated that although apoptosis can be curbed by use of chemical
inhibitors and genetic manipulation, their success is dependent on apoptotic stimuli. 相似文献
7.
Francisco J. Padillo Adolfo Cruz Carmen Navarrete Inmaculada Bujalance Javier Briceño José I. Gallardo 《Free radical research》2013,47(7):697-704
The induction of oxidative stress precedes liver injury during experimental obstructive jaundice (OJ). In this sense, different evidences suggest that melatonin (MEL), as antioxidant, may be useful in the protection against apoptosis and necrosis during experimental cholestasis. In addition, we will also assess if MEL-dependent protection is related to a recovery of antioxidant status disturbances induced by OJ. Cholestasis was achieved by double ligature and sectioning of the principal bile duct. MEL was injected intraperitoneally (500?μg/kg/day). Lipid peroxidation was evaluated by the measurement of malondialdehyde (MDA) content in liver. Different parameters related to antioxidant status, such as reduced glutathione (GSH), glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) were determined in liver. Liver injury was assessed by alanine aminotransferase (ALT) in serum, histological examination, DNA fragmentation and TUNEL assay. The activation of perisinusoidal stellate cells was evaluated by immunohistochemical measurement of α-smooth muscle actin in liver sections. The induction of OJ increased all the parameters related to apoptosis and necrosis in liver. The induction of liver injury was associated with stellate cell activation, as well as an increase in MDA (p<0.0001) and a reduction in GSH, GPx, catalase and SOD content (p<0.0001) in liver. MEL reduced hepatic apoptosis and necrosis (p<0.004) with a significant improvement in all oxidative stress markers. In conclusion, our results showed that MEL recovered the antioxidant status and reduced apoptosis and necrosis induced by experimental cholestasis. 相似文献
8.
Ekambaram Padmini Munuswamy Usha Rani 《Comparative biochemistry and physiology. Toxicology & pharmacology : CBP》2010,151(2):187-193
Induction of antioxidant proteins like thioredoxin (Trx) and heat shock protein 90α (HSP90α) is a crucial step in the cellular response to oxidative stress. Here, we report the impact of environmental stress on Trx and HSP90α expressions in freshly isolated hepatocytes of Mugil cephalus living in either a contaminated (Test; Ennore) or uncontaminated (Control; Kovalam) estuary. Modulation in the activities of signal transduction molecules like apoptosis signal-regulating kinase 1 (ASK1) and c-Jun NH2-terminal kinase 1/2 (JNK1/2) were also investigated to understand their functional role under natural stressed condition. The expression pattern of the proteins was determined by immunoblotting and the relationship between the proteins was identified by regression analysis. Test fish hepatocytes demonstrated significant upregulation (P < 0.05) in the levels of Trx and HSP90α and insignificant inductions in the expression pattern of ASK1 and JNK1/2 than control fish hepatocytes. These findings provide direct evidence that Trx and HSP90α induction in fish hepatocytes under stress may aid cell survival by negatively regulating ASK1 expression and thereby functionally antagonizing the apoptotic role of JNK1/2 in natural aquatic systems. 相似文献
9.
Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatocytes isolated from immature rainbow trout (Oncorhynchus mykiss) by collagenase perfusion were investigated with respect to induction of cytochrome P450 1A (CYP1A) enzyme activities and protein contents as well as DNA damage. Exposure of primary rainbow trout hepatocytes to TCDD resulted in increased CYP1A contents, as determined by immunoblotting, enhanced activities of 7-ethoxyresorufin-O-deethylase (EROD) and increased DNA damage as determined by the comet assay. By means of electron microscopy, no symptoms of cytotoxicity could be observed except for slight increases of lysosomal components and the smooth endoplasmic reticulum. Whereas CYP1A contents constantly increased over the duration of the entire experiment, EROD activities remained constant from day 3 of exposure to 1 nM TCDD; maximum induction of CYP1A activities was reached with 0.1 nM TCDD after 5 days. DNA damage increased in a time- and dose-dependent fashion until day 3. After 5 days, DNA damage was less pronounced, and the number of damaged nuclei declined in all TCDD concentrations. Since TCDD has been shown to not directly react with DNA, metabolism of TCDD or TCDD-induced changes in other metabolic pathways are suspected to result in the production of DNA-reactive (endogenous) substances. 相似文献
10.
In this study, autometallography and immunohistochemistry were used to localize and quantify cadmium and metallothionein (MT) levels, respectively, in cellular compartments of turbot liver on exposure to cadmium for 7 days and further depuration treatment for 14 days. Metals weakly bound to proteins (i.e. MTs) in hepatocyte lysosomes were visualized as black silver deposits (BSDs) using a light microscope. With the aid of a newly developed immunohistochemical procedure, MTs were localized and semi-quantified in both the cytosolic and the lysosomal compartments of hepatocytes. The BSD extent in the lysosomes of hepatocytes increased significantly as a result of cadmium exposure. This response was evidenced after 1h. Further, a progressive increase in the volume density of BSDs occurred up to the seventh day. Total MT immunohistochemical levels increased at a lower rate, starting after 1 day of cadmium exposure. BSD extent values recovered after depuration, whilst MT levels remain unchanged. It is possible that the detoxification rate of metals via lysosomes was diminished, whilst MT levels remained unchanged, at least after 14 days of depuration. It can be concluded that autometallography and MT immunohistochemistry are good tools for clarifying metal and metal-MT trafficking routes in hepatocytes, and also that BSD extent and MT immunohistochemical levels in the lysosomes and cytosol of fish hepatocytes can be considered to be useful biomarkers of metal exposure. 相似文献