Disease relevance of Cyc1

• Tacrolimus (FK506) attenuates biphasic cytochrome c release and Bad phosphorylation following transient cerebral ischemia in mice [1].
• Here we provide evidence that Optic Atrophy 1 (OPA1), a profusion dynamin-related protein of the inner mitochondrial membrane mutated in dominant optic atrophy, protects from apoptosis by preventing cytochrome c release independently from mitochondrial fusion [2].
• Moreover, cytochrome bd oxidase expression increased, but cytochrome c oxidase expression decreased slightly (nitric oxide) or not at all (hypoxia) [3].
• Infarct volumes and cytochrome c release also were less in Bid(-/-) mice (-67% and -41%, respectively) after mild focal ischemia [4].
• Mitochondria and cytochrome c release play a role in the death of neurons and glia after cerebral ischemia [4].

Psychiatry related information on Cyc1

• This study also suggests that these mitochondrial gene expression changes may relate to the role of mitochondrial dysfunction, oxidative damage, and cytochrome c in aging and in age-related diseases such as Alzheimer's disease and Parkinson's disease [5].
• Previously developed fast, selective optical sensors for detection of aqueous nitric oxide involved a protein, such as cytochrome c'. The new fluorescein derivative chemical sensors have characteristics similar to those of the protein-based biosensors, including fast response times, excellent selectivity, and complete reversibility [6].

High impact information on Cyc1

• Parl-/- mitochondria undergo faster apoptotic cristae remodeling and cytochrome c release [7].
• Mitochondria amplify activation of caspases during apoptosis by releasing cytochrome c and other cofactors [2].
• Specific ablation of the apoptotic functions of cytochrome C reveals a differential requirement for cytochrome C and Apaf-1 in apoptosis [8].
• As components of the apoptosome, a caspase-activating complex, cytochrome c (Cyt c) and Apaf-1 are thought to play critical roles during apoptosis [8].
• While cytochrome c release and DNA fragmentation are unaffected by the noncleavable p75 mutant, mitochondrial morphology of dying cells is maintained, and loss of plasma membrane integrity is delayed [9].

Chemical compound and disease context of Cyc1

• Therefore, fumarylacetoacetate apparently induces the release of cytochrome c, which in turn triggers activation of the caspase cascade in hepatocytes of subjects with hereditary tyrosinemia type 1 [10].
• Testosterone administration induced myocardial hypertrophy and accretion of RNA and protein without altering the DNA, and substantial increases in the activities of the lysosomal hydrolases and cytochrome c oxidase [11].
• N-benzyloxycarbonyl-val-ala-asp-fluoromethyl ketone (z-VAD.FMK), a nonselective caspase inhibitor, did not affect cytochrome c release after ischemia [12].
• Photosensitization of mitochondrial cytochrome c oxidase by hematoporphyrin derivative and related porphyrins in vitro and in vivo [13].
• Nitric oxide administered during hypoxia induced the release of cytochrome c, caspase-9 activation, and the loss of mitochondrial membrane potential followed by DNA fragmentation and lactate dehydrogenase release (markers of cell death) [14].

Biological context of Cyc1

• In the intrinsic pathway of apoptosis, mitochondria play a crucial role by releasing cytochrome c from the intermembrane space into the cytoplasm [15].
• AMR-induced apoptosis was accompanied by redistribution of cytochrome c from mitochondria to cytosol as well as down regulation of Bcl-2 and Bcl-X(L) proteins in a dose-dependent manner [16].
• Glutamate-induced apoptosis is also associated with intracellular [Ca(2+)]i overload, generation of reactive oxygen species (ROS), depression of cell energy metabolism, cytochrome c release, and increase in caspase-3 activity [17].
• Inhibition of caspases prevented DNA fragmentation but not cytochrome c release, indicating that mitochondrial disruption due to granzyme B is independent of caspase activation [18].
• Increased immunoreactivities for manganese superoxide dismutase, cytochrome c oxidase I, and apoptosis-inducing factor in the inner segment indicated mitochondrial oxidative stress [19].

Anatomical context of Cyc1

• We examined temporal profiles of survival-and death-related signals, Bad phosphorylation, release of cytochrome c (cyt.c), activation of caspase 3 and DNA fragmentation in the brain during and after middle cerebral artery occlusion (MCAo) in mice, and then examined the effect of tacrolimus on these signals [1].
• DADS induced apoptosis were accompanied by increased levels of Ca2+ and decreased mitochondrial membrane potential which then led to release the cytochrome c, cleavage of pro-caspase-3 [20].
• With the apoptotic model of murine-cerebral-derived microvascular endothelial cells (bEnd.3) induced by serum-free culture, we attempted to clarify the molecular mechanism of bEnd.3 apoptosis, particularly its relation to cytochrome C (Cyt C) [21].
• The resulting interaction leads to enzyme activation and rapid apoptosis in a variety of mammalian cell lines through a pathway involving mitochondrial events such as membrane depolarization (Deltapsim) and cytochrome c release [22].
• Hepatocyte survival was estimated by observing the stained mitochondria structure with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate fluorescence nick end labeling (TUNEL) method and antibodies against cytochrome C (Cyt-C) and caspase-3 [23].

Associations of Cyc1 with chemical compounds

• In WG, AICAR treatment increased HKII, GLUT4, cytochrome c, COX-1, and CS, and the alpha2-KO abolished the AICAR-induced increases, whereas no AICAR responses were observed in RG [24].
• In vivo administration of an ASMase inhibitor, imipramine, or ASMase knockdown by siRNA decreased ceramide generation during I/R, and attenuated serum ALT levels, hepatocellular necrosis, cytochrome c release, and caspase-3 activation [25].
• In cell-free extracts from brain and liver of Sprague-Dawley rats, caspase was activated by cytochrome c/2'-deoxyadenosine 5'-triphosphate at both neonatal and adult stages [26].
• The release of cytochrome c and activation of caspase-3 induced by NDGA were inhibited by NAC [27].
• AD 198-mediated Deltapsim and cytochrome c release are also unaffected by cellular treatment with either the mitochondrial permeability transition pore complex (PTPC) inhibitor cyclosporin A or the Ca chelators EGTA and BAPTA-AM [22].

Physical interactions of Cyc1

• The release of immune or gamma interferon (IFN-gamma) by major histocompatibility complex (MHC)-restricted pigeon cytochrome c-specific Lyt 1+2-, interleukin 2 (IL 2)-producing proliferative T cell clones when cultured with antigen and antigen-presenting cells (APC) is a sensitive measure of the state of activation of the cell [28].
• Clonal analysis of the major histocompatibility complex restriction and the fine specificity of antigen recognition in the T cell proliferative response to cytochrome C [29].
• These fractions were characterized by the presence of both monamine oxidase and cytochrome c oxidase activities and bound hexokinase [30].

Enzymatic interactions of Cyc1

• The NH(2)-terminal region of BID contains a caspase-8 (Casp-8) cleavage site and the cleaved form of BID translocates to mitochondrial membranes where it is a potent inducer of cytochrome c release [31].

Co-localisations of Cyc1

• Cleaved caspase-9 first appeared in the cytosol at 2 hours and colocalized with cytochrome c. Terminal deoxynucleotidyl transferase-mediated uridine 5;-triphosphate-biotin nick and labeling (TUNEL) showed significant increase of positive cells in Sod2 -/+ mice compared with the wild-type in the cortex, but not in the caudate putamen [32].

Regulatory relationships of Cyc1

• The PKC-delta inhibitor, rottlerin, and transfection with a transdominant-negative PKC-delta expression vector both inhibit AD 198 cytotoxicity through inhibition of Deltapsim and cytochrome c release [22].
• Cytochrome c and other nuclear-encoded mitochondrial genes are regulated by the transcription factor nuclear respiratory factor-1 (NRF-1) [33].
• Caspase-9 is activated in a cytochrome c-independent manner early during TNFalpha-induced apoptosis in murine cells [34].
• Moreover, although Bax-induced cytochrome c release was not dependent on tBid, the two proteins could function synergistically [35].
• Bax and Bak independently promote cytochrome C release from mitochondria [36].

Other interactions of Cyc1

• In addition to the death receptor-mediated pathway, TNF-induced apoptosis was further mediated by disruption of mitochondrial functions, characterized by release of cytochrome c and activation of caspase 9 [37].
• Moreover, evidence has been presented by confocal microscopy to show the translocation of Bax from cytosol to mitochondria in apoptotic hepatocyte, resulting in opening of permeability transition pores, which in turn decreases mitochondrial membrane potential and induces cytochrome c release into cytosol [38].
• Pathological relevance is demonstrated by the cytotoxic synergism between HAL and the Alzheimer disease-related peptide beta-amyloid(1-40), which correlates with Bcl-XS expression and its interaction with VDAC, and with cytosolic cytochrome c translocation [39].
• Inhibition of microvascular endothelial cell apoptosis by angiopoietin-1 and the involvement of cytochrome C [21].
• Bobel-16, Bobel-4, and Bobel-24 induced a caspase-independent cell death in K562 and Raji cells, accompanied by chromatin condensation, cytochrome c release, and dissipation of mitochondrial membrane potential in a concentration-dependent manner and production of reactive oxygen species [40].

Analytical, diagnostic and therapeutic context of Cyc1

• Apoptosis was assessed by TUNEL assay, caspase-3 cleavage, and cytochrome c release [41].
• Two major apoptotic signaling pathways have been defined in mammals, the extrinsic pathway, initiated by ligation of death receptors, and the intrinsic pathway, triggered by cytochrome c release from mitochondria [42].
• Serum leucine-rich alpha-2-glycoprotein-1 binds cytochrome c and inhibits antibody detection of this apoptotic marker in enzyme-linked immunosorbent assay [43].
• The present study aimed to evaluate the underlying mechanisms of apoptosis through modulation of Bax, Bcl-2 and cytochrome c protein expressions in a human pro-myelocytic leukemia (HL-60) cell line, as well as the potential of the CV extract as anti-leukemia agent using the athymic mouse xenograft model [44].
• Mouse testes contain a unique form of cytochrome c. As demonstrated by the indirect immunofluorescence technique, the testis-specific cytochrome c is detectable in the primary spermatocyte and in cell types comprising the later stages of spermatogenesis [45].

References