Age Changes in Amino Acid Incorporation by Rat Liver Microsomes

Hrachovec, Josef P.

doi:10.1159/000211674

Cited by 50 publications

(25 citation statements)

References 3 publications

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“…This kind of age change has been reported previously for liver by Hrachovec (12). Also, we have reported Isoprinosine reversal of other aspects of age change in polyribosomes elsewhere (7).…”

Section: Resultssupporting

confidence: 86%

“…The addition of poly(U) to polyribosomes from 11-month-old animal brain in a cell-free protein synthesizing system retarded the incorporation of ["CC]phenylalanine, although it contributes the phenylalanine codon. This paradoxical interaction of poly(U) with aging rat brain polyribosomes is a new finding and is probably related to messenger RNA ribosome interactions that change with age (12), rather than with codon properties. On the basis of our results, it is probable that poly(U), in the concentration employed, successfully competes with endogenous messenger RNA for ribosome binding sites, but that the intrinsic translation rate is retarded.…”

Section: Resultsmentioning

confidence: 89%

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Anti-Herpesvirus Action of Isoprinosine

Gordon

Ronsen

Brown

1974

Antimicrob Agents Chemother

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Anti-herpesvirus effects of Isoprinosine were found to be condition-dependent in vitro and in vivo. A herpes type 1 strain, grown in primary rabbit kidney cells, was not susceptible to Isoprinosine when cytopathic effect was evaluated, but was modestly inhibited when plaque-forming methocel overlay was used in the same cell line. However, the growth of a herpes type 2 strain was inhibited by Isoprinosine in this system when cytopathic effect was evaluated. Both viruses produced an encephalitis in hamsters after application by corneal abrasion. The encephalitis produced by a 1.5 mean lethal dose of herpesvirus was strikingly suppressed by large doses of Isoprinosine given ad libitum in the drinking water; this protection was not seen, however, at 15 mean lethal doses. Anti-herpes effects of Isoprinosine were suppressed by additional treatment with cortisone, both in tissue culture and in vivo. Isoprinosine, in the absence of virus infection, produced significant effects on the metabolism, structure, and function of brain ribosomes. In vivo, RNA components were labeled more rapidly and gave up their radioactivity more slowly after treatment with Isoprinosine. This enhanced cytoplasmic radioactivity was associated with a loss of incorporated radioactivity located in the nucleus and an increase in radioactivity located in a ribonucleoprotein fraction >4S and <18S. Ribosomes from treated brains gave physical evidence of being more compact (less orthochromic). Isoprinosine treatment increased the incorporation of ["CC]phenylalanine into nascent protein in a cell-free system examining protein synthesis in brain polyribosomes. The addition of the exogenous messenger ribonucleic acid, polyuridylic acid, produced a significant age-dependent inhibition in the incorporation of [IC ] phenylalanine. This inhibition was significantly greater when ribosomes were isolated from animals pretreated with Isoprinosine. These and other observations suggest that the Isoprinosine stimulation of host ribonucleic acid metabolism may be coupled to the production of ribosomes that do not effectively translate exogenous messenger ribonucleic acid.Isoprinosine (methisoprinol, NPT-10381) was first reported by us (8,9), and then by others (4, 17), to exert antiviral activity in vitro and in vivo. In the present study, we determine the conditions that permit a generation of antiviral effects by Isoprinosine against herpes simplex virus in tissue culture systems and in one standard in vivo system, hamster encephalitis.Although the mechanism of antiviral action of Isoprinosine is not yet understood, we have previously reported effects of the drug on the rapid incorporation of RNA and protein precursors into polyribosomes of uninfected and influenza virus-infected monkey kidney cells (8,9), and in uninfected rat brain (7). In the present 'Present address:

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Section: Resultssupporting

confidence: 86%

Section: Resultsmentioning

confidence: 89%

Anti-Herpesvirus Action of Isoprinosine

Gordon

Ronsen

Brown

1974

Antimicrob Agents Chemother

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“…According to the present knowledge, the most general sign of cellular aging may be the slowing down of protein synthesis as compared to the young cells (Buetow and Gandhi, 1973;Hrachovec, 1969;Mainwaring, 1969;Kanungo et al, 1970). Old cells reach the same levels of enzyme activity in induction experiments only after much longer periods of time than young ones (Adelman, 1971(Adelman, , 1972Adelman et al, 1977;Samis et al, 1972).…”

Section: Discussionmentioning

confidence: 99%

Effects of Centrophenoxine on the Monovalent Electrolyte Contents of the Large Brain Cortical Cells of Old Rats

Zs.‐Nagy¹,

Pieri²,

Giuli³

et al. 1979

Gerontology

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The effect of centrophenoxine has been studied on the monovalent electrolyte contents of the brain cortical cells of old female Wistar rats by means of energy dispersive x-ray microanalysis. The drug was administered in form of an intraperitoneal injection of 100 mg/kg body weight for 20 days. The treatment decreased the potassium content in both the nucleus and cytoplasm in terms of dry mass fraction, whereas the sodium concentration remained unchanged. The Na⁺/K⁺ ratio increased significantly in both cell compartments. The chloride content of the nuclei decreased slightly. If one supposes just 1–2% rehydration of the old cytoplasm, the decrease of the total ionic strength may be of considerable extent, it may even reach the values obtained in young adult animals. The results are interpreted in terms of a recently developed ‘membrane hypothesis’ of aging (Zs.-Nagy: J. theor. Biol., 1978, in press).

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“…It is well known that protein turnover is lower in adults and older individuals than it is in younger ones (Sharp et , 1957). Hrachovec (1969) has demonstrated the decreased ability of cell free systems to incorporate amino acids into liver microsomes with advancing age. Hrachovec (1969) suggests that a gradual accumulation of inhibitors in the cell sap and microsomal vesicles causes a gradual feedback repression of protein synthesis at the site of translation, which in turn represses RNA synthesis.…”

Section: Cell Fractionation Studymentioning

confidence: 99%

“…Hrachovec (1969) has demonstrated the decreased ability of cell free systems to incorporate amino acids into liver microsomes with advancing age. Hrachovec (1969) suggests that a gradual accumulation of inhibitors in the cell sap and microsomal vesicles causes a gradual feedback repression of protein synthesis at the site of translation, which in turn represses RNA synthesis. While it can be argued that an accumu lation of protein inhibitors in the endoplasmic reticulum with advancing age would decrease the RNA/protein ratio, a repression of RNA synthesis would also decrease this ratio.…”

Section: Cell Fractionation Studymentioning

confidence: 99%

Age changes in the canine pancreas: histomorphological, electron microscopic, and biochemical study

Saladino¹,

Charles²

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Age Changes in Amino Acid Incorporation by Rat Liver Microsomes

Cited by 50 publications

References 3 publications

Anti-Herpesvirus Action of Isoprinosine

Anti-Herpesvirus Action of Isoprinosine

Effects of Centrophenoxine on the Monovalent Electrolyte Contents of the Large Brain Cortical Cells of Old Rats

Age changes in the canine pancreas: histomorphological, electron microscopic, and biochemical study

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