Involvement of peripheral-type benzodiazepine receptors in the intracellular transport of heme and porphyrins.

Involvement of peripheral-type benzodiazepine receptors in the intracellular transport of heme and porphyrins. Research Abstract Details 

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Involvement of peripheral-type benzodiazepine receptors in the intracellular transport of heme and porphyrins. Abstract Text:

S Taketani,H Kohno,T Furukawa,R Tokunaga,

To investigate the involvement of peripheral-type benzodiazepine receptors (PBR) in heme metabolism, we examined the interaction of [55Fe]heme with PBR. Transfection of the cloned mouse PBR-isoquinoline carboxamide-binding protein (PBR/IBP) cDNA into monkey kidney Cos-1 cells resulted in a 2.5-fold increase in [55Fe]hemin binding sites, concomitant with the increase in [3H]PK11195 binding sites, as compared with those seen in antisense PBR/IBP cDNA-transfected cells. The binding of hemin to the transfected receptors exhibited a relatively high affinity with a Kd of 12 nM, and was inhibited by several benzodiazepine ligands, including PK11195, Ro 5-4864, diazepam and protoporphyrin IX. When mouse liver mitochondria were incubated with [55Fe]hemin, the binding to PBR had a Kd of 15 +/- 1.8 nM. The Bmax of [55Fe]hemin binding to the mitochondria was 6.88 +/- 0.76 pmol/mg of protein, a value consistent with that of [3H]PK11195 binding, with a lower affinity. Coproporphyrinogen III, a precursor porphyrin produced in the cytosol, is translocated into mitochondria, then is converted to protoporphyrinogen IX; this conversion decreased in the presence of benzodiazepine ligands. To examine whether this decrease was related to a decrease in the binding of coproporphyrinogen to the mitochondria, the effects of benzodiazepines on the binding of coproporphyrinogen were examined. As the binding was dose-dependently inhibited by PK11195, Ro 5-4864, and diazepam, porphyrins are likely to be endogenous ligands for PBR. We propose that PBR play a role in the intracellular transport of porphyrins and heme.

Involvement of peripheral-type benzodiazepine receptors in the intracellular transport of heme and porphyrins. Publishing Authors By Initials

S Taketani,H Kohno,T Furukawa,R Tokunaga,

For similar investigative techniques: genetic techniques: gene transfer techniques: transfection research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transfection research

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Involvement of peripheral-type benzodiazepine receptors in the intracellular transport of heme and porphyrins. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of biochemistry

VOLUME: 117

Page Numbers: 875-80

Journal Abbreviation: J. Biochem.

ISSN: 0021-924X

DAY: 19

MONTH: Apr

YEAR: 1995

Involvement of peripheral-type benzodiazepine receptors in the intracellular transport of heme and porphyrins. Information

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LANGUAGE: eng

NlmUniqueID: 376600

Involvement of peripheral-type benzodiazepine receptors in the intracellular transport of heme and porphyrins. Keywords Mesh Terms:

KEYWORDS: Transfection

MESH TERMS: metabolism

Chemical & Substance for Abstract: Involvement of peripheral-type benzodiazepine receptors in the intracellular transport of heme and porphyrins. Information

Substance Name: Iron

Registry Number: 7439-89-6

Grant and Affiliation Information for Involvement of peripheral-type benzodiazepine receptors in the intracellular transport of heme and porphyrins.

AFFILIATION: Department of Hygiene, Kansai Medical University, Osaka.

Country: JAPAN

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MEDLINETA: J Biochem

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