Production of Membrane Whorls in Rat Liver by Some Inhibitors of Protein Synthesis

Abstract

Inhibitors of protein synthesis capable of differential effects on nascent peptide synthesis on membrane-bound and free polyribosomes were employed to investigate the structure and function of cellular membranes of liver. The formation of membranous whorls in the cytoplasm and distension of nuclear membranes were induced by inhibitors of protein synthesis (i.e., cycloheximide and emetine) which predominantly interfere with nascent peptide synthesis on membrane-bound polyribosomes in situ. Other inhibitors of protein synthesis such as puromycin and fusidic acid, which inhibit nascent peptide synthesis on both free and membranebound polyribosomes, and chloramphenicol, which inhibits mitochondrial protein synthesis, did not induce these alterations. Cycloheximide, puromycin, and chloramphenicol produce some common cellular lesions as reflected by similar alterations in morphology, such as swelling of mitochondria, degranulation of rough endoplasmic reticulum, and aggregation of free ribosomes. The process of whorl formation in the cytoplasm, the incorporation of [3H]leucine and of [3H]choline into endoplasmic reticulum and the total NADPH-cytochrome c reductase activity of the endoplasmic reticulum were determined. During maximum formation of membranous whorls, pH]leucine incorporation into cytoplasmic membranes was inhibited, while [3H]choline incorporation into these structures was increased; maximum inhibition of protein synthesis and stimulation of choline incorporation into endoplasmic reticulum, however, preceded whorl formation. Cycloheximide decreased the activity of NADPH-cytochrome c reductase of rough endoplasmic reticulum, but increased NADPH-cytochrome c reductase activity of smooth endoplasmic reticulum. In addition, cycloheximide decreased the content of hemoprotein in both the microsomal and mitochondrial fractions of rat liver, and the activities of mixed function oxidase and of oxidative phosphorylation were impaired to different degrees. Succinate-stimulated microsomal oxidation was also inhibited. The possible mechanisms involved in the formation of membranous whorls, as well as their functions, are discussed.

Effect of cycloheximide on the freezing tolerance and ultrastructure of cortical parenchyma cells from mulberry twigs

“…In other words, low temperature may play an important role as a trigger in inducing synthesis of some proteins concerned with cold acclimation in the cells of twigs collected in mid-or late October. Hwang et al (1974) showed that in rat liver CHI effectively inhibited nascent peptide synthesis on membrane-bound polysomes, and they observed that CHI produced some cellular lesions: degranulation and membrane whorls of rER. Noguchi and Ueda (1979) observed in the cell cycle of Micrasterias crux melitensis that lobe bifurcation at the cell developmental stage after nuclear division advanced only one step in the presence of CHI, and that the production of vesicles from dictyosomes was specifically inhibited.…”

Protein-synthesis inhibition induces perichromatin granule accumulation and intranuclear rodlet formation in osmotically stimulated supraoptic neurons

“…Although dilated cisterns of RER have been reported in some SON neurons of dehydrated rats (Morris and Dyball 1974; Tweedle and Hatton 1977), the changes in the RER reported here represent a generalized response in SON cells of the cycloheximide-treated rats, with the profuse branching of RER cisterns being the essential ultrastructural feature. Since cycloheximide selectively inhibits nascent peptide synthesis on membrane-bound polyribosomes (Vazquez 1979), the alteration of the RER is a reliable criterion of cycloheximide effect, as indicated in liver cells exposed to this proteinsynthesis inhibitor (Hwang et al 1974). Indeed, in SON neurons, Zambrano and de Robertis (1967) have reported large-scale cisternal swelling of the rough endo- Previous studies have documented the existence in PGs of small nuclear 4.7S RNA and hnRNP, a precursor ofmRNAs, as well as snRNPs (Daskal et al 1975;Fakan et al 1984;Puvion et al 1984).…”

Cellular mechanisms of toxicity and tolerance in the copper‐loaded rat. I. Ultrastructural changes in the liver

“…Membranous whorl formation has previously been described in copper intoxication in the rat (12) and during the prehaemolytic phase in the sheep (7), and has been interpreted as an adaptative phenomenon in view of their appearance during recovery from injuries (23) and in regenerative in cirrhotic livers (24). The presence Of membrane whorls is associated with an imbalance in pr0tein:phospholipids synthesis in favour of the latter (25). (22).…”