The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria.

The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria. Research Abstract Details 

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The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria. Abstract Text:

Tamara Azarashvili,Dmitry Grachev,Olga Krestinina,Youri Evtodienko,Igor Yurkov,Vassilios Papadopoulos,Georg Reiser,

The peripheral-type benzodiazepine receptor (PBR) is an 18 kDa mitochondrial membrane protein with still elusive function in cell death. Here, we studied whether PBR is involved in Ca2+-induced permeability transition pore (PTP) opening in isolated rat brain mitochondria (RBM). PTP opening is important in mitochondrial events leading to programmed cell death. Immunoblots revealed a single 18 kDa anti-PBR antibody-immunoreactive band in purified RBM. Adenine nucleotide transporter, a key PTP component, was found in the PBR-immunoprecipitate. In isolated intact RBM, addition of a specific anti-PBR antibody [H. Li, Z. Yao, B. Degenhardt, G. Teper, V. Papadopoulos, Cholesterol binding at the cholesterol recognition/interaction amino acid consensus (CRAC) of the peripheral-type benzodiazepine receptor and inhibition of steroidogenesis by an HIV TAT-CRAC peptide, Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 1267-1272] delayed Ca2+-induced dissipation of membrane potential (psi(m)) and diminished cyclosporine A-sensitive Ca2+ efflux, which are both indicative for the suppression of PTP opening. Moreover, anti-PBR antibody caused partial retention of Ca2+ in the mitochondrial matrix in spite of psi(m) dissipation, and reduced activation of respiratory rate at Ca2+-induced PTP opening. A release of pro-apoptotic factors, AIF and cytochrome c, from RBM was shown at threshold Ca2+ load. Anti-PBR antibody blocked the release of AIF but did not affect the cytochrome c release. Addition of ATP was able to initiate PTP closing, associated with psi(m) restoration and Ca2+ re-accumulation. At the same time mitochondrial protein phosphorylation (incorporation of 32P from [gamma-32P]ATP) occurred and anti-PBR antibody was able to inhibit phosphorylation of these proteins. The endogenous PBR ligand, protoporphyrin IX, facilitated PTP opening and phosphorylation of the mitochondrial proteins, thus, inducing effects opposite to anti-PBR antibody. This study provides evidence for PBR involvement in PTP opening, controlling the Ca2+-induced Ca2+ efflux, and AIF release from mitochondria, important stages of initiation of programmed cell death.

The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria. Publishing Authors By Initials

T Azarashvili,D Grachev,O Krestinina,Y Evtodienko,I Yurkov,V Papadopoulos,G Reiser,

For similar proteins: membrane proteins: receptors, cell surface: receptors, neurotransmitter: receptors, amino acid: receptors, gaba: receptors, gaba-a research abstracts see: proteins: membrane proteins: receptors, cell surface: receptors, neurotransmitter: receptors, amino acid: receptors, gaba: receptors, gaba-a research

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The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria. Journal Published:

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

Journal: Cell calcium

VOLUME: 42

Page Numbers: 27-39

Journal Abbreviation: Cell Calcium

ISSN: 0143-4160

DAY: 15

MONTH: 12

YEAR: 2006

The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8006226

The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria. Keywords Mesh Terms:

KEYWORDS: Receptors, GABA-A

MESH TERMS: physiology

Chemical & Substance for Abstract: The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria. Information

Substance Name: Mitochondrial ADP, ATP Translocases

Registry Number: 9068-80-8

Grant and Affiliation Information for The peripheral-type benzodiazepine receptor is involved in control of Ca2+-induced permeability transition pore opening in rat brain mitochondria.

AFFILIATION: Institut für Neurobiochemie, Otto-von-Guericke-Universität Magdeburg, Medizinische Fakultät, Leipziger Strasse 44, 39120 Magdeburg, Germany.

Country: Scotland

AGENCY: United States NIEHS

GRANT: ES-07447

ACRONYM: ES

MEDLINETA: Cell Calcium

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