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FURTHER EVALUATION OF POLYPEPTIDE SYNTHESIS IN CEREBRAL ANOXIA, HYPOXIA AND ISCHEMIA
Authors:Kazuyoshi  Morimoto Joan  Brengman Takehiko  Yanagihara
Institution:Department of Neurology. Mayo Clinic and Mayo Medical School, Rochester. MN 55901, U.S.A.
Abstract:The alteration of polypeptide synthesis was evaluated with microsomes isolated from anoxic rabbit, hypoxic rat and ischemic gerbil brains to estimate the extent of functional or structural changes in polyribosomes in situ and the extent of artifact during tissue preparation. By using two-stage experimentation with combination of control and pathological microsomes and supernatant, it was found that the previously observed effects on microsomal or polyribosomal polypeptide synthesis in the above pathophysiological conditions were mainly the reflection of the alteration of polyribosomes in situ rather than the artifact during tissue preparation by degradative processes. In support of this finding. the use of inhibitors of degradative enzymes did not significantly protect microsomes either in normal or in pathological conditions. It was noted that the decline of tissue pH, to a certain extent, could be correlated with dysfunction of polyribosomes both in situ and during tissue preparation in cerebral hypoxia and anoxia. Since there is little change in ATP level, it was postulated that the alteration of pH in situ is responsible for the observed suppression of polypeptide synthesis in vitro at least in cerebral hypoxia. This hypothesis was supported by the subsequent experiments with incubation of brain slices and homogenization of brain tissue under various pH. It was emphasized that the environmental biochemical elements surrounding polyribosomes in cytoplasm should be evaluated as possible contributing factors for polyribosomal dysfunction in such pathological conditions as cerebral anoxia, hypoxia or ischemia if the alteration of energy state does not explain the phenomenon entirely.
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