Influence of Warm Ischemia Time on Peripheral-Type Benzodiazepine Receptor: A New Aspect of the Role of Mitochondria

Doucet, Christelle; Zhang, Keqiang; Desurmont, Thibault; Hébrard, William; Scépi, M.; Nadeau, Cedric; Cau, Jérôme; Leyre, P.; Febrer, Guillaume; Carretier, Michel; Richer, Jean; Papadopoulos, Vassilios; Hauet, Thierry; Burucoa, Christophe; Goujon, Jean Michel

doi:10.1159/000105139

Cited by 5 publications

(2 citation statements)

References 60 publications

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“…First, we demonstrated that TAC resulted in a 3-fold increase in expression of the TSPO in WT animals (Fig. 1F,G ), an upregulation of TSPO that parallels that seen in cardiac ischemia and reperfusion 29 and under stress conditions in other tissues 27 , 28 , 30 . Pressure overload for 8 weeks in WT animals resulted in the expected changes in cardiac morphology, function, and metabolism associated with HF (see Figs 2 and 3 , and Table 1 ).…”

Section: Discussionmentioning

confidence: 62%

Cardiac-specific Conditional Knockout of the 18-kDa Mitochondrial Translocator Protein Protects from Pressure Overload Induced Heart Failure

Thai

Daugherty

Frederich

et al. 2018

Sci Rep

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Heart failure (HF) is characterized by abnormal mitochondrial calcium (Ca2+) handling, energy failure and impaired mitophagy resulting in contractile dysfunction and myocyte death. We have previously shown that the 18-kDa mitochondrial translocator protein of the outer mitochondrial membrane (TSPO) can modulate mitochondrial Ca2+ uptake. Experiments were designed to test the role of the TSPO in a murine pressure-overload model of HF induced by transverse aortic constriction (TAC). Conditional, cardiac-specific TSPO knockout (KO) mice were generated using the Cre-loxP system. TSPO-KO and wild-type (WT) mice underwent TAC for 8 weeks. TAC-induced HF significantly increased TSPO expression in WT mice, associated with a marked reduction in systolic function, mitochondrial Ca2+ uptake, complex I activity and energetics. In contrast, TSPO-KO mice undergoing TAC had preserved ejection fraction, and exhibited fewer clinical signs of HF and fibrosis. Mitochondrial Ca2+ uptake and energetics were restored in TSPO KO mice, associated with decreased ROS, improved complex I activity and preserved mitophagy. Thus, HF increases TSPO expression, while preventing this increase limits the progression of HF, preserves ATP production and decreases oxidative stress, thereby preventing metabolic failure. These findings suggest that pharmacological interventions directed at TSPO may provide novel therapeutics to prevent or treat HF.

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Section: Discussionmentioning

confidence: 62%

Cardiac-specific Conditional Knockout of the 18-kDa Mitochondrial Translocator Protein Protects from Pressure Overload Induced Heart Failure

Thai

Daugherty

Frederich

et al. 2018

Sci Rep

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“…The pig seems to be the ideal species to serve this purpose. 1 Several porcine models to study mechanisms of WI, CI and IRI exist: reperfusion models 2,3 , isolated organ preservation systems 4,5 and kidney transplantation models. [6][7][8][9] However, the technical and surgical aspects of these models and their possible pitfalls have not been described in detail.…”

Section: Introductionmentioning

confidence: 99%

Reproducible Model for Kidney Autotransplantation in Pigs

Jochmans

Lerut

Heedfeld

et al. 2009

Transplantation Proceedings

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Peripheral Benzodiazepine Receptors in Health and Disease

Hadjiivanova

2009

Biotechnology & Biotechnological Equipment

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Two main types of benzodiazepine receptors have been identified: central type, which is found in the brain mainly in the cortex, limbic areas and cerebellum, and peripheral type, which is found in the kidneys, lungs, ovaries, testes, adrenal glands and blood cells, but is also present in the CNS, in particular in glial cells. Peripheral benzodiazepine receptors (PBR) are detected in most of the animals including insects, mollusks, pisces, amphibians, aves, mammals, and as well in various plants and bacteria. PBR are involved in apoptosis, proliferation, porphyrin transport, immunomodulation, and many other processes, such as steroidogenesis in adrenal glands, brain, male and female gonads, biological adaptation to stress, etc. Subcellularly, PBR are predominantly localized on the outer mitochondrial membrane and are part of a complex that consists of three components: 18 kDa receptor protein, 32 kDa voltage-dependent anion channel and 30 kDa adenine nucleotide carrier. Only 18 kDa receptor protein was assigned as PBR. In steroid synthesizing tissues, PBR control cholesterol import from the outer to the inner mitochondrial membranes and is vital for steroid biosynthesis. PBR in plants as Arabidopsis are also involved in steroid transport in mitochondria. In normal brain, PBR are localised in mitochondria of glial cells and expressed in very low concentrations. Their expression rises after microglial activation following brain injury and inflammation. Changes in the level of PBR have been observed in neurological and psychiatric disorders including multiple sclerosis, Alzheimer's, Parkinson's and Huntington's diseases. Stress affects PBR bidirectionally: acute stress is associated with increased PBR density, whereas chronic stress down-regulates PBR. The PBR ligands control cell proliferation and differentiation, and several cancers including breast, colon, ovary, liver have been associated with increased PBR number. In aged animals and humans PBR in adrenals, kidneys, testes, lymphocytes, and brain are differentially changed probably due to malfunctioning of PBR.

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Influence of Warm Ischemia Time on Peripheral-Type Benzodiazepine Receptor: A New Aspect of the Role of Mitochondria

Cited by 5 publications

References 60 publications

Cardiac-specific Conditional Knockout of the 18-kDa Mitochondrial Translocator Protein Protects from Pressure Overload Induced Heart Failure

Cardiac-specific Conditional Knockout of the 18-kDa Mitochondrial Translocator Protein Protects from Pressure Overload Induced Heart Failure

Reproducible Model for Kidney Autotransplantation in Pigs

Peripheral Benzodiazepine Receptors in Health and Disease

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