Alteration in Microsomal Protein Synthesis During Early Development of Mouse Brain

Abstract

Abstract.-The loss of protein synthesis during early mouse-brain development was shown to be the result, at least in part, of the inability of microsomes obtained from more mature neural tissue to participate in rapid polypeptide synthesis. The loss of brain microsomal activity was observed shortly after birth and continued until the animals were approximately ten days old. Despite the difference in synthetic activity, sucrose gradient profiles of microsomes and polyribosomes from young and more mature brain tissue were quite similar. The loss in protein synthesis was shown to be independent of available mRNA and not attributable to aminoacyl-RNA synthetases and tRNA binding activity.Introduction.-Several studies have indicated that the rates of macromolecular synthesis are altered during maturation of mammalian brain tissue. Higher rates of protein synthesis in younger brain tissue have been observed both in vivo and in vitro. 16 We have reported that both protein and RNA synthesis undergo a rapid decrement during early development of mouse brain tissue. The loss of protein synthesis during this critical period of development has been shown to be the results of a change in an intracellular component rather than an alteration in cellular membrane permeability.7 The present report involves an investigation of the identity of the intracellular component that is responsible, at least in part, for this altered rate of macromolecular synthesis. The role of microsomes and polyribosomes in this developmental phenomenon is described and compared to similar studies with brain and other mammalian tissues.

Protein Synthesis in Ehrlich Ascites Cells

“…In the 14-day-old tumor, the ribosomes are especially deficient in RNA, and the possibility of defective ribosomes is further suggested by the inability of poly U to stimulate the cell-free amino acid incorporating system to the level of exponentially growing cells. The situation may be analogous to the one described in mouse brain by Johnson & Belytschko (1969) who found that the decreased amino acid incorporating activity occurring in mouse brain after birth can only be attributed to a change in the ribosome particle.…”

Cerebral ischemia in gerbils: polyribosomal function during progression and recovery.

“…The second peak designated as dimer (D) has a modal S value of 140 according to the calculation formula of McEwen. 16 There was little difference in the size distribution profiles after extended centrifugation of postmitochondrial supernatant for 16 h or when the sample was homogenized in the presence of bentonite (1 mg/ml), a known inhibitor of ribonuclease. An addition of heparin (0.5 mg/ml), another inhibitor of ribonuclease, resulted in partial degradation of polyribosomes to ribosomal subunits.…”

“…Polypeptide synthesis was carried out in the incubation medium consisting of 50 mM Tris-HCl buffer, pH 7.4, 50 mM KC1, 10 mM MgCl 2 , 10 mM 2-mercaptoethanol, 2 mM ATP, 0.2 mM GTP, 10 mM phosphoenolpyruvate, 16 For polypeptide synthesis with microsomes, 0.3 mg of microsome protein and 0.5 mg of pH 5 factor were added. For polyribosomes, 0.4 A^ units of polyribosome and 2.0 A^,, units of pH 5 factor were added.…”

Changes in Brain Protein Synthesis during the Life Span of Male Fischer Rats

“…Cell-Free protein synthesis by the PMS from rat brain was determined using optimum conditions that are similar to conditions reported previously (13,17). The homogenization buffer was supplemented with 2 mAf ATP, 0.5 mAf GTP, 14.8 mAf creatine phos phate, 0.2 mg/ml creatine phosphokinase, 1 jiCi/ml of (3H)-/.-valine (specific acitivity 2 Ci/mmol), a mixture of ¿-amino acids lacking valine (at a concentration of 50 pM for each amino acid), and Sephadex G-25 chromatographed PMS.…”

“…A decrease in brain protein synthesis during development has been well established and has been observed in rats (1,5,21,24), mice (12,13) and chickens (25). The decrease in brain protein synthesis during development has been shown to occur primarily during the first 30 days after birth (5,12,16,21,25); however, brain protein synthesis appears to decrease further after 30 days of age (5,25).…”