TRANSPORT OF HISTONE THROUGH THE BLOOD-BRAIN-BARRIER

  • 1 December 1989
    • journal article
    • research article
    • Vol. 251  (3) , 821-826
Abstract
The present studies were designed to determine if the endogenous cationic protein, e.g., histone, is capable of penetrating the blood-brain barrier (BBB) in vivo. Calf thymus histone was iodinated with [125I]iodine and was found to be taken up rapidly by isolated bovine brain capillaries used as an in vitro model system of the BBB via a time- and temperature-dependent mechanism. The binding was saturable and a Scatchard plot of the binding data was linear, yielding a KD = 15.2 .+-. 2.8 .mu.M and a maximal binding = 7.7 .+-. 1.0 nmol/mg of protein. Other polycations such as protamine or polylysine markedly inhibited uptake of [125I]histone, but cationized immunoglobulin caused no inhibition of bovine brain capillary uptake of [125I]histone. The in vivo brain VD of [125I]histone reached 159 .+-. 70 .mu.l/g by 10 min of carotid arterial perfusion as compared to the 10-min VD for [3H]albumin, 17 .+-. 7 .mu.l/g. Most of this uptake represented sequestration by the vasculature, but approximately 8% of the total histone taken up by brain was found to be transported unmetabolized (based on trichloroacetic acid precipitability of brain supernatant ([125I]) into brain interstitium). These studies demonstrate that histone is transported through the BBB in vivo via absorptive-mediated transport. Thus, histone is an endogenous protein that is capable of transport through the BBB and may be a potential vector for pharmaceutical delivery through the BBB.

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