The Beneficial Effect of Phosphocreatine Accumulation in the Creatine Kinase Transgenic Mouse Liver in Endotoxin-Induced Hepatic Cell Death

Kanazawa, Akiyoshi; Iwata, Satoru; Satoh, Seiji; Hatano, Etsuro; Shinohara, Hisashi; Kitai, Toshiyuki; Shoji, Takuhito; Ikai, Iwao; Yamamoto, Masayuki; Takahashi, Rei; Chance, Britton; Yamaoka, Yoshio

doi:10.1006/jsre.1998.5482

Cited by 13 publications

(9 citation statements)

References 27 publications

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“…1B), are also overexpressed in some tumors. Although little is known about the role of ANT isoforms or PBR in the regulation of apoptosis, it appears that mitochondrial creatine kinase can confer apoptosis resistance (and inhibition of the PTPC) in the presence of creatine [40]. Perhaps more importantly, the expression of the tumor suppressor protein Bax is frequently compromised in carcinomas, and a large portion of human tumors overexpress Bcl-2-like oncoproteins [41], emphasizing that the composition and/or control of the PTPC is drastically altered in malignancy.…”

Section: Deficient Apoptosis In Cancer Cells-a Mitochondrial Defect?mentioning

confidence: 98%

Pathophysiology of mitochondrial cell death control

Vieira¹,

Kroemer²

1999

Cellular and Molecular Life Sciences (CMLS)

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Mitochondria have been recently recognized to play a major role in the control of apoptosis or programmed cell death. Permeabilization of mitochondrial membranes, a decisive feature of early cell death, is regulated by members of the Bcl-2 family which interact with the permeability transition pore complex (PTPC). Thus, the cytoprotective oncoprotein Bcl-2 stabilizes the mitochondrial membrane barrier function, whereas the tumor suppressor protein Bax permeabilizes mitochondrial membranes. The regulation of membrane permeabilization is intertwined with that of the bioenergetic and redox functions of mitochondria. The implications of alterations in the composition of the PTPC and in mitochondrial function for the pathophysiology of cancer (reduced apoptosis) and neurodegeneration (enhanced apoptosis) are discussed.

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Section: Deficient Apoptosis In Cancer Cells-a Mitochondrial Defect?mentioning

confidence: 98%

Pathophysiology of mitochondrial cell death control

Vieira¹,

Kroemer²

1999

Cellular and Molecular Life Sciences (CMLS)

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“…60 Creatine and creatine phosphate may have cytoprotective effects in some models of cell death. 61,62 The protein kinase src…”

Section: Peripheral Benzodiazepin Receptormentioning

confidence: 99%

Permeabilization of the mitochondrial inner membrane during apoptosis: impact of the adenine nucleotide translocator

et al. 2000

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Mitochondrial membrane permeabilization can be a rate limiting step of apoptotic as well as necrotic cell death. Permeabilization of the outer mitochondrial membrane (OM) and/or inner membrane (IM) is, at least in part, mediated by the permeability transition pore complex (PTPC). The PTPC is formed in the IM/OM contact site and contains the two most abundant IM and OM proteins, adenine nucleotide translocator (ANT, in the IM) and voltage-dependent anion channel (VDAC, in the OM), the matrix protein cyclophilin D, which can interact with ANT, as well as apoptosis-regulatory proteins from the Bax/Bcl-2 family. Here we discuss that ANT has two opposite functions. On the one hand, ANT is a vital, specific antiporter which accounts for the exchange of ATP and ADP on IM. On the other hand, ANT can form a non-specific pore, as this has been shown by electrophysiological characterization of purified ANT reconstituted into synthetic lipid bilayers or by measuring the permeabilization of proteoliposomes containing ANT. Pore formation by ANT is induced by a variety of different agents (e.g. Ca 2+ , atractyloside, thiol oxidation, the pro-apoptotic HIV-1 protein Vpr, etc.) and is enhanced by Bax and inhibited by Bcl-2, as well as by ADP. In isolated mitochondria, pore formation by ANT leads to an increase in IM permeability to solutes up to 1500 Da, swelling of the mitochondrial matrix, and OM permeabilization, presumably due to physical rupture of OM. Although alternative mechanisms of mitochondrial membrane permeabilization may exist, ANT emerges as a major player in the regulation of cell death.

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“…Another possible cause for inconsistent findings might be compensatory up-regulation of CK expression in pathological liver tissue. Two lines of evidence that favour this hypothesis are: (i) partially hepatectomized rat liver was reported to show an increase in BB-CK activity (see [22]); and (ii) overexpression of CK isoenzymes in the liver of transgenic mice was shown to stabilize energy metabolism under low-oxygen stress and after a metabolic challenge [23,24], to accelerate regeneration of liver mass following major hepatectomy [10,25], and to increase endotoxin tolerance [5,26]. …”

Section: Introductionmentioning

confidence: 99%