Peri‐ and postnatal development of heterogeneity in the amounts of endoplasmic reticulum in mouse hepatocytes

Kanai, Kazuo; Kanamura, Shinsuke; Watanabe, Jun

doi:10.1002/aja.1001750406

Cited by 20 publications

(21 citation statements)

References 28 publications

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“…This possibility is a matter for future studies. Interestingly, the ontogenic expression of hepatic AQP8 also coincides with the hormonally controlled maturation of the mouse hepatocyte SER.32, 49 The mouse liver AQP9 has recently been shown to be regulated at a transcriptional level coordinately by the plasma concentrations of insulin in accordance with the nutritional condition, such as fasting and refeeding. Whether SER AQPS is regulated by hormones controlling the metabolism of hepatic glucose is an exciting matter for future studies.…”

Section: Discussionmentioning

confidence: 99%

Ontogeny, distribution, and possible functional implications of an unusual aquaporin, AQP8, in mouse liver

Ferri¹

2003

Hepatology

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Aquaporins are channel proteins widely expressed in nature and known to facilitate the rapid movement of water across numerous cell membranes. A mammalian aquaporin, AQPS, was recently discovered and found to have a very distinct evolutionary pathway. To understand the reason for this divergence, here we define the ontogeny and exact subcellular localization of AQPS in mouse liver, a representative organ transporting large volumes of water for secretion of bile. Northern blotting showed strong AQPS expression between fetal day 17 and birth as well as at weaning and thereafter. Interestingly, this pattern was confirmed by immunohistochemistry and coincided both temporally and spatially with that of hepatic glycogen accumulation. As seen by reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, fasting was accompanied by remarkable down-regulation of hepatic AQPS that paralleled the expected depletion of glycogen content. The level of hepatic AQPS returned to be considerable after refeeding. Immunoelectron microscopy confirmed AQPS in hepatocytes where labeling was over smooth endoplasmic reticulum (SER) membranes adjacent to glycogen granules and in canalicular membranes, subapical vesicles, and some mitochondria. In conclusion, in addition to supporting a role for AQPS in canalicular water secretion, these findings also suggest an intracellular involvement of AQPS in preserving cytoplasmic osmolality during glycogen metabolism and in maintaining mitochondrial volume. AQPS may have evolved separately to feature these intracellular roles as no other known aquaporin shows this specialization. (HEPATOLOGY 2003;38:947-957.) quaporins are a family of proteinaceous channels widely distributed in a range of living organisms A from bacteria to humans, where they mediate the osmotic movement of water across biological membranes.' Aquaporins are being shown to be involved in physiologic processes of central importance, including se- cretion and absorption of fluids in the gastrointestinal and reproductive tracts, renal water handling, fluid balance in the lung and brain, maintenance of fluid and ionic homeostases in the inner ear,2 and preserving corneal transparency.3 Aquaporins also have pathophysiologic relevance because they have been found in humans to underlie severe forms of nephrogenic diabetes in~ipidus,~ defective urinary concentrating,5 and congenital cataracts,6 and their involvement in the pathogenesis of many other clinical conditions with altered fluid homeostasis is under intense investigation. Among the 1 1 aquaporins (AQPO-AQP 10) that have so far been recognized in mammals, AQP8 represents a very distinctive homologue as indicated by the striking divergence of its evolutionary pathway.' However, the reasons for this phylogenetic divergence are obscure. AQP8 was recently cloned from rat,8,9 mouse,1° and human' ' tissues. By heterologous expression in Xenopw hevis oocytes, the rat8,9 and human' ' AQP8 channels were found to be selectively permeable to water, whereas the mouse...

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Section: Discussionmentioning

confidence: 99%

Ontogeny, distribution, and possible functional implications of an unusual aquaporin, AQP8, in mouse liver

Ferri¹

2003

Hepatology

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“…However, these studies did not distinguish between periportal and perivenular hepatocytes. Kanai et al (1986a) found that the area of SER per unit cytoplasmic volume increases only slightly in periportal hepatocytes between 17-day-old fetuses and adult mice (Fig. 4).…”

Section: Sermentioning

confidence: 90%

“…Kanai et al (1986a) observed that the area of RER per unit cytoplasmic volume does not change in either periportal and perifollowing a n overnight mating. (Reproduced from Kanai et al, 1986a, with permission of the publisher.) venular hepatocytes during development except (1) just before birth and (2) between 20 days of age and adulthood (Fig.…”

Section: Hepatocyteorganelles Rer and Golgi Complexmentioning

confidence: 96%

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Fine structure and function of hepatocytes during development

Kanamura

Kanai

Watanabe

1990

J. Elec. Microsc. Tech.

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This paper reviews the fine structure and function of hepatocytes during fetal and postnatal development. Bile canaliculi develop to a mature appearance during perinatal and early postnatal periods, while bile secretory function is immature at birth and develops during the postnatal period. The rough endoplasmic reticulum is prominent and remains unchanged in amount during development, and the Golgi complex is large from early stages of fetal life. The smooth endoplasmic reticulum (SER) appears shortly before birth and increases in quantity to the adult level after birth. In mouse hepatocytes, Sv (area per unit cytoplasmic volume) of SER increases in perivenular cells between 1 and 10 days of age, although it remains low in periportal cells. Similarly, Sv of total ER increases in both periportal and perivenular cells between 1 and 5 days of age and then becomes greater in perivenular than periportal cells. This suggests that the postnatal increase in the drug-metabolizing capacity occurs predominantly in perivenular hepatocytes. SER proliferates after phenobarbital (PB) administration in both perivenular and periportal cells in 3-, 5-, and 10-day-old mice, and predominantly in perivenular cells in 20-day-old and adult mice. Thus the conspicuous proliferation of SER in perivenular hepatocytes after PB administration, characteristic of adult liver, becomes manifest during postnatal development. In mouse hepatocytes, Vv (volume per unit cytoplasmic volume) of mitochondrial matrix and peroxisomes and Sv of mitochondrial inner membrane and cristae increase in both periportal and perivenular cells between birth and 10 days of age. Then, Vv of mitochondrial matrix remains unchanged in periportal cells but decreases in perivenular cells. In general, the process of postnatal hepatocyte differentiation appears to include several phases of development; cell organelles develop during the early postnatal period, subsequently the cells undergo both functional and structural heterogeneity, and the late postnatal period after weaning is the time for a marked increase in cell size.

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“…The typical adult pattern of predominantly one cell thickness is not established in the human until about five years of age in the child (Morgan & Hartort 1961;Macsween 1994). During the postnatal period, there are also increases in hepatocyte size, average diameter hepatic lobules and quantity of endoplasmic reticulum (Kanai et al 1986;Kanamura et al 1990;Macsween 1994). Sinusoidal fenestrations increase in density in the early postnatal period, coincident with the establishment of zonation of hepatocellular metabolic activity within the acinus (Barbera-Guillem et al 1986).…”

Section: Hepatic Physiologymentioning

confidence: 99%

Neonatal Hepatic Drug Elimination

Gow

Ghabrial

Smallwood

et al. 2001

Pharmacology & Toxicology

104

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After the transition from in utero to newborn life, the neonate becomes solely reliant upon its own drug clearance processes to metabolise xenobiotics. Whilst most studies of neonatal hepatic drug elimination have focussed upon in vitro expression and activities of drug-metabolising enzymes, the rapid physiological changes in the early neonatal period of life also need to be considered. There are dramatic changes in neonatal liver blood flow and hepatic oxygenation due to the loss of the umbilical blood supply, the increasing portal vein blood flow, and the gradual closure of the ductus venosus shunt during the first week of life. These changes which may well affect the capacity of neonatal hepatic drug metabolism. The hepatic expression of cytochromes P450 1A2, 2C, 2D6, 2E1 and 3A4 develop at different rates in the postnatal period, whilst 3A7 expression diminishes. Hepatic glucuronidation in the human neonate is relatively immature at birth, which contrasts with the considerably more mature neonatal hepatic sulfation activity. Limited in vivo studies show that the human neonate can significantly metabolise xenobiotics but clearance is considerably less compared with the older infant and adult. The neonatal population included in pharmacological studies is highly heterogeneous with respect to age, body weight, ductus venosus closure and disease processes, making it difficult to interpret data arising from human neonatal studies. Studies in the perfused foetal and neonatal sheep liver have demonstrated how the oxidative and conjugative hepatic elimination of drugs by the intact organ is significantly increased during the first week of life, highlighting that future studies will need to consider the profound physiological changes that may influence neonatal hepatic drug elimination shortly after birth.The development of clinical pharmacology has resulted in a more rational approach to drug therapy, as well as a deeper understanding of the factors capable of influencing drug disposition, and hence drug effects. Of these factors, age is of great importance. However, substantial differences in drug disposition not only exist between neonates and adults, but also among premature neonates, term neonates, infants and children.During the last two decades drug disposition in the neonatal period has been studied extensively. A major impetus for these studies seems to have been a series of incidents involving illness or death following the administration of drugs at ratios of dose/body weight innocuous in an adult (Craft et al. 1974;Gershanik et al. 1982). These studies have shown that the transition from neonate to childhood is characterised by the ontogeny of all of the processes of drug absorption, distribution, hepatic metabolism and renal excretion, with the development of hepatic drug metabolism being particularly important.The extent to which the neonatal drug-metabolising en-

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Peri‐ and postnatal development of heterogeneity in the amounts of endoplasmic reticulum in mouse hepatocytes

Cited by 20 publications

References 28 publications

Ontogeny, distribution, and possible functional implications of an unusual aquaporin, AQP8, in mouse liver

Ontogeny, distribution, and possible functional implications of an unusual aquaporin, AQP8, in mouse liver

Fine structure and function of hepatocytes during development

Neonatal Hepatic Drug Elimination

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