Apoptosis and Human Diseases: Mitochondrion Damage and Lethal Role of Released Cytochrome c as Proapoptotic Protein

Caroppi, Paola; Sinibaldi, Federica; Fiorucci, Laura; Santucci, Roberto

doi:10.2174/092986709789378206

Cited by 172 publications

(120 citation statements)

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“…Caspases are the key proteins that modulate the apoptotic response. Caspase-3 is activated by an initiator caspase such as caspase-9 during mitochondrion-mediated apoptosis, which is a key executioner of apoptosis (32,33).…”

Section: Discussionmentioning

confidence: 99%

Millimeter wave radiation induces apoptosis via affecting the ratio of Bax/Bcl-2 in SW1353 human chondrosarcoma cells

Ye²,

Cai³

et al. 2011

Oncol Rep

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Abstract. The efficacy and safety of millimeter wave radiation has been proven for various types of malignant tumors. However, the mechanisms underlying effects of millimeter wave radiation on apoptosis are still unclear. The present study was undertaken to examine the effects of millimeter wave radiation on cell apoptosis and mitochondrial membrane potential, and to determine the molecular mechanism of millimeter wave radiation-induced apoptosis by investigating the expression of Bcl-2 family proteins (Bcl-2, Bax), caspase-9 and caspase-3 in SW1353 cells. We found that millimeter wave radiation suppressed the viability of SW1353 cells, demonstrating that millimeter wave radiation induced cell apoptosis and reduced cell viability in a time-dependent manner. Furthermore, we observed that treatment of cells with millimeter wave radiation significantly induced loss of mitochondrial membrane potential, upregulated proapoptotic Bax, caspase-9 and caspase-3, but did not significantly change levels of antiapoptotic Bcl-2. These data suggested that millimeter wave radiation may induce apoptosis via affecting the ratio of Bax/Bcl-2 in SW1353 cells.

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Section: Discussionmentioning

confidence: 99%

Millimeter wave radiation induces apoptosis via affecting the ratio of Bax/Bcl-2 in SW1353 human chondrosarcoma cells

Ye²,

Cai³

et al. 2011

Oncol Rep

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“…CL-bound cyt c shows tertiary structural rearrangements, which include alteration of the heme pocket region and detachment of M80 from the sixth coordination position of the heme iron [3][4][5][6]. The CL-specific peroxidase action acquired by membrane-bound cyt c in the early stages of apoptosis, which initiates the protein pro-apoptotic activity, is critical for cells; CL peroxidation induces cyt c release into the cytosol and favors the accumulation of products releasing pro-apoptotic factors [7][8][9][10]. This explains why considerable effort has been made over recent years to clarify the mechanisms governing the cyt c-CL interaction and the (cyt c-CL) complex stability.…”

Section: Introductionmentioning

confidence: 99%

The effects of ATP and sodium chloride on the cytochrome c–cardiolipin interaction: The contrasting behavior of the horse heart and yeast proteins

Sinibaldi¹,

Droghetti²,

Polticelli³

et al. 2011

Journal of Inorganic Biochemistry

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In cells a portion of cytochrome c (cyt c) (15-20%) is tightly bound to cardiolipin (CL), one of the phospholipids constituting the mitochondrial membrane. The CL-bound protein, which has nonnative tertiary structure, altered heme pocket, and disrupted Fe(III)-M80 axial bond, is thought to play a role in the apoptotic process. This has attracted considerable interest in order to clarify the mechanisms governing the cyt c-CL interaction. Herein we have investigated the binding reaction of CL with the c-type cytochromes from horse heart and yeast. Although the two proteins possess a similar tertiary architecture, yeast cyt c displays lower stability and, contrary to the equine protein, it does not bind ATP and lacks pro-apoptotic activity. The study has been performed in the absence and in the presence of ATP and NaCl, two compounds that influence the (horse cyt c)-CL binding process and, thus, the pro-apoptotic activity of the protein. The two proteins behave differently: while CL interaction with horse cyt c is strongly influenced by the two effectors, no effect is observed for yeast cyt c. It is noteworthy that NaCl induces dissociation of the (horse cyt c)-CL complex but has no influence on that of yeast cyt c. The differences found for the two proteins highlight that specific structural factors, such as the different local structure conformation of the regions involved in the interactions with either CL or ATP, can significantly affect the behavior of cyt c in its reaction with liposomes and the subsequent pro-apoptotic action of the protein.

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“…In the first, ligandbound membrane receptors such as CD95/Fas/APO-1 recruit and oligomerize the adaptor protein and procaspase-8, followed by caspase-8 processing (Salvesen and Dixit, 1999). In the second pathway, apoptosis is triggered by a change in mitochondrial permeability that results in the release of cytochrome c Garrido et al, 2006;Caroppi et al, 2009). Once cytochrome c binds its cytosolic partner Apaf-1, the human homologue of the apoptotic protein CED-4, to form an oligomeric Apaf-1-cytochrome c complex in an ATP/dATP-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

Cdk2 acts upstream of mitochondrial permeability transition during paclitaxel-induced apoptosis

et al. 2011

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Sequential activation of cyclin-dependent kinases (Cdks) controls mammalian cell cycle. Here we demonstrate that the upregulation of cyclin-dependent kinase 2 (Cdk2) activity coincides with the loss of mitochondrial membrane potential (MMP) in paclitaxel-induced apoptosis. Ectopic expression of the dominant negative Cdk2 (Cdk2-dn) and a specific Cdk2 inhibitor, p21 WAF1/CIP1 , effectively suppresses the loss of MMP, the release of cytochrome c, and subsequent activation of caspase-3 in paclitaxel-treated cells. Whereas forced activation of Cdk2 by overexpression of cyclin A dramatically promotes these events. We further show that Cdk2 activation status does not interfere with a procedure that lies downstream of cytochrome c release induced by Bax protein. These findings suggest that Cdk2 kinase can regulate apoptosis at earlier stages than mitochondrial permeability transition and cytochrome c release.

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Apoptosis and Human Diseases: Mitochondrion Damage and Lethal Role of Released Cytochrome c as Proapoptotic Protein

Cited by 172 publications

References 0 publications

Millimeter wave radiation induces apoptosis via affecting the ratio of Bax/Bcl-2 in SW1353 human chondrosarcoma cells

Millimeter wave radiation induces apoptosis via affecting the ratio of Bax/Bcl-2 in SW1353 human chondrosarcoma cells

The effects of ATP and sodium chloride on the cytochrome c–cardiolipin interaction: The contrasting behavior of the horse heart and yeast proteins

Cdk2 acts upstream of mitochondrial permeability transition during paclitaxel-induced apoptosis

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