Localization of cytochrome b5 in rat organs and tissues by immunohistochemistry

Tavassoli, Mehdi; Ozols, Juris; Sugimoto, G.; Cox, K.; Müller‐Eberhard, Ursula

doi:10.1016/0006-291x(76)90991-8

Cited by 20 publications

(3 citation statements)

References 11 publications

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“…The NADPH-generating enzymes, glucose-6-phosphate dehydrogenase (27,28,36), malic enzyme (33), and isocitrate dehydrogenase (24,25,27,28), are predominant in perivenous hepatocytes ( Table 1). This is also the case with NADPH-utilizing enyzmes NADPHcytochrome c reductase (49), cytochrome P450 (50, 51), cytochrome bg (52), and NAD(P)H-tetrazolium reductases (24,53) which can be regarded as nonphysiological side activities of monooxygenases. Moreover, NADPHcytochrome c reductase (49) and cytochrome P450 (50) as well as the smooth endoplasmic reticulum can be preferentially induced in the perivenous zone by barbiturates.…”

Section: Biotransformationmentioning

confidence: 98%

Functional Hepatocellular Heterogeneity

2007

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Hepatocytes from the periportal (afferent) and perivenous (efferent) zones of the liver parenchyma differ in their enzyme content and subcellular structures. Therefore, different functions are proposed for the two zones. (a) Oxidative energy metabolism, /3-oxidation, amino acid catabolism, ureagenesis from amino acids, gluconeogenesis, bile acid, and bilirubin excretion and oxidation protection are preferentially located in the periportal zone. (b) Glycolysis, liponeogenesis, ureagenesis from ammonia, and biotransformation are predominantly situated in the perivenous zone. Heterogeneity in the synthesis of plasma proteins also appears to exist.The heterogeneous expression of the genome in hepatocytes is apparently caused by the periportal to perivenous gradient in oxygen and hormone concentrations, and by a different autonomic innervation of the parenchymal zones.The liver consists of parenchymal and nonparenchymal cells (e.g., Kupffer, endothelial, bile ductule, and connective tissue cells). The parenchymal hepatocytes appear to be rather uniform histologically; histochemically they reveal differences. This heterogeneity has been known for many years, first on a descriptive (1, 2), then increasingly on a functional level (3). The metabolic heterogeneity of liver parenchymal cells has been reviewed recently (4, 5). It is the goal of the following account to summarize the present knowledge of parenchymal heterogeneity and, thereby, to contribute to the understanding of basic liver functions in health and disease. LIVER STRUCTUREThe structural unit which connects parenchymal and nonparenchymal liver cells to a functional unit is still controversial. The classical lobule, in its most recent "sickle zone" modification (6), is characterized by a surface-like inflow of blood directly from the portal tract forming sickle zones of hemodynamic equipotential. The acinus (7), in contrast, is defined by a linear inflow of blood forming berry-type structures of hemodynamic equipotential around the vascular axis of an afferent vessel. Following the bloodstream, at least two different zones can be discerned both in the acinus and sickle zone lobules: the periportal (afferent) zone, which is supplied I Heterogeneity of liver parenchyma appears to be similar in all mammals. Therefore, this article was concentrated to a review of studies mainly with rats.This work was supported by grants from the Deutsche Forschungsgemeinschaft, D-5300 Bonn, Germany.Address reprint requests to: Professor Dr. Kurt Jungermann, Institut fiir Biochemie, Fachbereich Medizin, Georg-August-Universitat, Humboldtallee 7, D-3400 Gottingen, Germany.with oxygen-, substrate-, and hormone-rich blood, and the perivenous (efferent) zone, which receives blood poor in oxygen, substrates, and hormones but enriched in COZ and other products. Since the quality of the blood changes during liver passage it may be assumed that cells in the different zones of the liver parenchyma, whichever functional organization it might have, should possess different structures, enzyma...

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Section: Biotransformationmentioning

confidence: 98%

Functional Hepatocellular Heterogeneity

2007

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“…In contrast, no effect on the déméthylation of l4C-AP was ob served in AA-treated rats with periportal he patic damage since the parameters character izing the elimination of 14C 0 2 in breath were very close to the corresponding values in con trol rats (table I). This observation can be explained by the finding reported by several investigators that cytochrome P-450, which mediated the déméthylation of l4C-AP, is located predominantly in hepatocytes of the centrilobular region [6][7][8], In agreement with this interpretation is the finding in the present study demonstrating that when the hepatic damage induced by AA extended beyond the periportal region, involving most of the hepatic lobule, the déméthylation of l4C-AP was affected as indicated by the changes in the l4C 0 2 exhalation-time curve ( fig. 2).…”

Section: Discussionmentioning

confidence: 73%

“…For exam ple. it has been shown that the concentration of the components of the microsomal drugmetabolizing enzyme system, such as cyto chrome P-450 and cytochrome b5, is higher in hepatocytes of the centrilobular region than in those on the periphery of the same hepatic lobule [6][7][8][9]. These findings may sug gest that hepatic cells in different lobular zones have different functions.…”

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confidence: 79%

Aminopyrine Breath Test and Zonal Hepatic Damage in Rats

Farag¹,

Volicer²

1985

Pharmacology

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Acute hepatic damage in centrilobular or periportal areas was induced in two groups of rats by intraperitoneal injections of bromobenzene or allyl alcohol, respectively. The effect of this zonal damage on the demethylation of ¹⁴C-aminopyrine was evaluated by measuring the elimination of ¹⁴CO₂ in breath following intravenous administration of a tracer dose of the labeled compound. In rats with centrilobular hepatic damage ¹⁴CO₂ elimination in breath was significantly decreased compared to controls. In rats with periportal hepatic damage, elimination of ¹⁴CO₂ in breath was unchanged. These results suggest functional heterogeneity of hepatocytes in vivo with respect to drug-metabolizing capacity.

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