Induction of autophagy by amino-acid deprivation in perfused rat liver

Mortimore, Glenn E.; Schworer, Charles M.

doi:10.1038/270174a0

Cited by 314 publications

(178 citation statements)

References 26 publications

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“…The factor initiating the formation of the autophagic vacuoles by compounds of such widely different chemical compositions as those above is unknown. However, in liver their formation is stimulated by amino-acid deprivation (Mortimer and Schworer 1977). It is of interest that along with the development of these vacuoles there is concomitant inhibition of mitotic activity in the cells of the follicle bulbs.…”

Section: Discussionmentioning

confidence: 99%

Effects of Internally Administered N-[5-( 4-Aminophenoxy)Pentyl]Phthalimide on Wool Follicles and Skin of Sheep

Chapman¹,

Rigby²

1980

Aust. Jnl. Of Bio. Sci.

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When N-[5-(4-aminophenoxy)pentyl]phthalimide was administered to sheep in sufficient quantities to permit manual removal of the fleece (400 mg/kg body weight orally, or 75 mg/kg body weight intravenously during a period of 48 h), cell division ceased in the wool follicle bulbs within 1 day. Dark-staining bodies (autophagic vacuoles) developed concomitantly in the cytoplasm of the bulb cells. The nuclei of cells in the keratogenous zones of the fibres became pycnotic 2 days after dosing and subsequent keratinization of these portions of the fibres was impaired. All the follicles retrogressed prior to day 7 after dosing, and the root ends which formed on the fibres moved towards the skin surface, reaching the level of the sebaceous glands by day 7. At this time mitotic activity recommenced around the dermal papillae in about 50% of the follicles. A small number of tips of new fibres emerged from the skin surface of some of the depilated sheep by day 14. The root ends on the fibres in the fleeces harvested at days 7-15 were fragmented with various degrees of taper. By 21 days, most follicles were growing emergent fibres. Thickening of the epidermis, increase in sebaceous gland size and decrease in skin thickness occurred in some of the depilated sheep.Smaller doses of the compound (200 mg/kg body weight orally or 40 mg/kg body weight intravenously during 24 h) produced weakness in the wool. Fewer autophagic vacuoles were present in follicle bulbs 1 day after dosing and not all follicles regressed. The weakened region of the fleece contained a mixture of shed fibre ends and continuously growing fibres with thin regions proximal to poorly keratinized lengths of fibre. No change was observed in other components of the skin of the sheep with weakened wool.The follicular changes produced by this compound are similar in some respects to those produced by other depilatory compounds or that occur during natural cyclic hair growth.

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Section: Discussionmentioning

confidence: 99%

Effects of Internally Administered N-[5-( 4-Aminophenoxy)Pentyl]Phthalimide on Wool Follicles and Skin of Sheep

Chapman¹,

Rigby²

1980

Aust. Jnl. Of Bio. Sci.

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“…Inhibition of adenylate cyclase activity could thus explain the unchanged CAMP concentrations after vinblastine injection in his study despite the possible inhibition of CAMP phosphodiesterase activity, which could otherwise lead to increased CAMP concentrations as in the pituitary [lo]. Unchanged CAMP levels have also been observed in autophagocytosis induced by amino acid deprivation in perfused rat liver, when glycogen was simultaneously frequently found in AV [5].…”

Section: Biochemical Assaysmentioning

confidence: 98%

Vinblastine‐induced autophagocytosis: effects on liver glycogen

Hirsimäki

1983

FEBS Letters

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The possible similarities of the mechanism by which vinblastine induces autophagocytosis in liver were compared with the known effects of glucagon in glucagon‐induced autophagocytosis. A single intraperitoneal injection of vinblastine produced a wave of autophagocytosis in <0.5 h in mouse hepatocytes. Liver glycogen content decreases simultaneously and blood glucose first increased and then decreased below control values. Both liver cAMP concentration and the activity of glycogen phosphorylase remained unchanged. These findings provide evidence tht the induction of autophagocytosis after vinblastine injection is not mediated by cAMP. The increased degradation of glycogen may occur in the lysosomal system by means of increased autophagocytosis.

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“…62,63 One target of these signals is the serine threonine protein kinase Tor (Target of rapamycin), a phosphorylated kinase that inhibits the autophagic process until it is dephosphorylated. The first evidence that Tor has a role in regulating autophagy came from experiments involving rat hepatocytes that showed that rapamycin partially reverses the inhibitory effects of amino acids on autophagic proteolysis.…”

Section: Regulation Of Autophagymentioning

confidence: 99%

Autophagy and multivesicular bodies: two closely related partners

2008

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In the majority of cell types, multivesicular bodies (MVBs) are a special kind of late endosomes, crucial intermediates in the internalization of nutrients, ligands and receptors through the endolysosomal system. ESCRT-0, I, II and III (endosomal sorting complex required for transport) are involved in the sorting of proteins into MVBs, generating the intraluminal vesicles. Autophagy is a lysosomal degradation pathway for cytoplasmic components such as proteins and organelles. The autophagosome, a well-characterized structure of the autophagy pathway, can fuse with endocytic structures such as MVBs to generate the amphisome. Finally, the amphisome fuses with the lysosome to degrade the material wrapped inside. Currently, clear evidence suggests that efficient autophagic degradation requires functional MVBs. This review highlights the most recent advances in our understanding of the molecular machinery that participates in MVB biogenesis and regulates the interplay between autophagy and this organelle.

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Induction of autophagy by amino-acid deprivation in perfused rat liver

Cited by 314 publications

References 26 publications

Effects of Internally Administered N-[5-( 4-Aminophenoxy)Pentyl]Phthalimide on Wool Follicles and Skin of Sheep

Effects of Internally Administered N-[5-( 4-Aminophenoxy)Pentyl]Phthalimide on Wool Follicles and Skin of Sheep

Vinblastine‐induced autophagocytosis: effects on liver glycogen

Autophagy and multivesicular bodies: two closely related partners

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