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Cyclophilin D-sensi...
Cyclophilin D-sensitive mitochondrial permeability transition in adult human brain and liver mitochondria.
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- Hansson, Magnus (författare)
- Lund University,Lunds universitet,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine
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- Morota, Saori (författare)
- Lund University,Lunds universitet,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine
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Chen, Li (författare)
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Matsuyama, Nagahisa (författare)
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Suzuki, Yoshiaki (författare)
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Nakajima, Satoshi (författare)
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Tanoue, Tadashi (författare)
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Omi, Akibumi (författare)
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Shibasaki, Futoshi (författare)
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Shimazu, Motohide (författare)
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Ikeda, Yukio (författare)
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Uchino, Hiroyuki (författare)
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- Elmer, Eskil (författare)
- Lund University,Lunds universitet,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine
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(creator_code:org_t)
- Mary Ann Liebert Inc, 2011
- 2011
- Engelska.
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert Inc. - 1557-9042 .- 0897-7151. ; 28, s. 143-153
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Abstract
Ämnesord
Stäng
- The mitochondrial permeability transition (mPT) is considered to be a major cause of cell death under a variety of pathophysiological conditions of the CNS and other organs. Pharmacological inhibition or genetic knock-out of the matrix protein cyclophilin D (CypD) prevents mPT and cell degeneration in several models of brain injury. Provided that findings in animal models can be translatable to human disease, pharmacological inhibition of mPT offers a promising therapeutic target. The objective of this study was to validate the presence of a CypD-sensitive mPT in adult human brain and liver mitochondria. In order to perform functional characterization of human mitochondria, fresh tissue samples were obtained during hemorrhage or tumor surgery and mitochondria were rapidly isolated. Mitochondrial calcium retention capacity, a quantitative assay for mPT, was significantly increased by the CypD inhibitor cyclosporin A in both human brain and liver mitochondria, whereas thiol-reactive compounds and oxidants sensitized mitochondria to calcium-induced mPT. Brain mitochondria underwent swelling upon calcium overload, which was reversible upon calcium removal. To further explore mPT of human mitochondria, liver mitochondria were demonstrated to exhibit several classical features of the mPT phenomenon such as calcium-induced loss of membrane potential and respiratory coupling, as well as release of the pro-apoptotic protein cytochrome c. It is concluded that adult viable human brain and liver mitochondria possess an active CypD-sensitive mPT. The present findings support the rationale of CypD and mPT inhibition as pharmacological targets in acute and chronic neurodegeneration.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
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- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Hansson, Magnus
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Morota, Saori
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Chen, Li
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Matsuyama, Nagah ...
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Suzuki, Yoshiaki
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Nakajima, Satosh ...
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visa fler...
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Tanoue, Tadashi
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Omi, Akibumi
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Shibasaki, Futos ...
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Shimazu, Motohid ...
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Ikeda, Yukio
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Uchino, Hiroyuki
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Elmer, Eskil
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Neurologi
- Artiklar i publikationen
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Journal of Neuro ...
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Lunds universitet