Cytochrome <i>c</i> release and caspase activation in hydrogen peroxide‐ and tributyltin‐induced apoptosis

Stridh, Hélène; Kimland, Monica; Jones, Dean P.; Orrenius, Sten; Hampton, Mark B.

doi:10.1016/s0014-5793(98)00630-9

Cited by 245 publications

(146 citation statements)

References 28 publications

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“…[52][53][54] These effects are due to opening of the pore complex on the mitochondrial membrane, which in normal circumstances shows a close conformation. The changes of the mitochondrial structure induce several functional alterations (collapse of the mitochondrial inner membrane potential, uncoupling of the respiratory chain, overproduction of ROS, release of ions and proteins), leading to apoptosis or necrosis.…”

Section: Discussionmentioning

confidence: 99%

Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug‐resistant colon carcinoma cells (LoVo) than on their wild‐type counterparts

Calcabrini¹,

Arancia²,

Marra³

et al. 2002

Intl Journal of Cancer

122

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The occurrence of resistance to cytotoxic agents in tumor cells, associated with several phenotypic alterations, is one of the major obstacles to successful anticancer chemotherapy. A new strategy to overcome MDR of human cancer cells was studied, using BSAO, which generates cytotoxic products from spermine, H 2 O 2 and aldehyde(s). The involvement of these products in causing cytotoxicity was investigated in both drug-sensitive (LoVo WT) and drug-resistant (LoVo DX) colon adenocarcinoma cells. Evaluation of clonogenic cell survival showed that LoVo DX cells are more sensitive than LoVo WT cells. Fluorometric assay and treatments performed in the presence of catalase demonstrated that the cytotoxicity was due mainly to the presence of H 2 O 2 . Cytotoxicity was eliminated in the presence of both catalase and ALDH. Transmission electron microscopic observations showed more pronounced mitochondrial modifications in drug-resistant than in drug-sensitive cells. Mitochondrial functionality studies performed by flow cytometry after JC-1 labeling revealed basal hyperpolarization of the mitochondrial membrane in LoVo DX cells. After treatment with BSAO and spermine, earlier and higher mitochondrial membrane depolarization was found in LoVo DX cells than in drug-sensitive cells. In addition, higher basal ROS production in LoVo DX cells than in drug-sensitive cells was detected by flow-cytometric analysis, suggesting increased mitochondrial activity in drug-resistant cells. Our results support the hypothesis that mitochondrial functionality affects the sensitivity of cells to the cytotoxic enzymatic oxidation products of spermine, which might be promising anticancer agents, mainly against drug-resistant tumor cells.

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Section: Discussionmentioning

confidence: 99%

Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug‐resistant colon carcinoma cells (LoVo) than on their wild‐type counterparts

Calcabrini¹,

Arancia²,

Marra³

et al. 2002

Intl Journal of Cancer

122

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“…Recently, it was reported that eosinophils contain a small number of mitochondria-like structures, lacking functional respiration, but with a suggested role to participate in the apoptotic process [17]. Tributyltin (TBT) is a potent inducer of caspase activation and apoptosis in human leukaemia T cell lines and human peripheral T lymphocytes [18][19][20][21][22]. The caspase activation is preceded by early mitochondrial changes, including rapid loss of mitochondrial membrane potential (Dy m ) and release of cytochrome c. Preincubation with the adenine nucleotide translocator (ANT)-inhibitor, bongkrekic acid (BA), blocked TBT-induced mitochondrial changes and apoptosis in Jurkat cells, suggesting that TBT induces mitochondrial permeability transition (MPT) specifically in these cells [21].…”

Section: Discussionmentioning

confidence: 99%

“…The Dy m was measured every 5 min for 20 min. TBTtreated purified lymphocytes were used as positive control cells, as it has been described previously that TBT reduces the Dy m in these cells [18]. The granulocytes were also tested for their response to the mitochondrial uncoupler carbonyl cyanide m-chlorophenyl hydrazone (CCCP) (Sigma Chemical Co, St Louis, MO, USA), a well-characterized agent known to dissipate Dy m in many cell types.…”

Section: Mitochondrial Membrane Potentialmentioning

confidence: 99%

Caspase activation in the absence of mitochondrial changes in granulocyte apoptosis

Nopp¹,

Lundahl²,

Stridh

2002

Clinical and Experimental Immunology

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SUMMARY Eosinophils and neutrophils are two different types of granulocytes evolved from a common haematopoetic precursor in the bone marrow. Eosinophils are mainly involved in parasitic infection and allergic inflammation while neutrophils mainly participate in the defence against bacterial infections. Prolongation of granulocyte life span by inhibition of apoptosis may lead to tissue load of cells, and this has been detected in different inflammatory reactions. The molecular mechanisms and the potential role of the mitochondria in granulocyte apoptosis are poorly understood. In the present study we have characterized further the role of the mitochondria in granulocyte-apoptosis by studying the sequence of mitochondrial permeability transition (MPT) induction, loss of mitochondrial membrane potential (Δψm) and release of cytochrome c. This was made possible by applying tributyltin (TBT), a well-characterized apoptotic stimulus and MPT-inducer. We also studied potential differences in apoptosis-susceptibility between eosinophils and neutrophils. Ten minutes of TBT-exposure resulted in a substantial caspase-3 activity in both eosinophils and neutrophils, followed by phosphatidylserine (PS)-exposure after 30–120 min. Interestingly, caspase-3 activity was not preceded by MPT-induction, loss of Δψm or by cytochrome c-release in either eosinophils or neutrophils. In conclusion, we have demonstrated an extremely rapid induction of caspase-3 activity and apoptosis in human blood granulocytes without prior mitochondrial changes, including loss of mitochondrial membrane potential and release of cytochrome c. Our results open the possibility for a mitochondrial-independent activation of caspase 3 and subsequent apoptosis in granulocytes.

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“…In addition, apoptosis, one of the mechanisms of cell death, is closely related to TNFα (30). TBT induces apoptosis in several kinds of cells (13)(14)(15)(16)(17)(18). We hypothesized that TBT induces apoptosis in macrophages, and that the mechanism of the apoptosis induced by TBT is related to TNFα or c-jun.…”

Section: Discussionmentioning

confidence: 99%

“…Low levels of TBT induced cell death of lymphocytes. TBT has induced apoptosis and caspase activation in human leukemia T cells (14,15), peripheral T lymphocytes (16) and rat thymocytes (17,18). However, little is known about the immunotoxicity of TBT compounds for macrophages.…”

Section: Introductionmentioning

confidence: 99%

Tributyltin (TBT) increases TNFα mRNA expression and induces apoptosis in the murine macrophage cell line in vitro

Nakano

Tsunoda

Konno

2004

Environ Health Prev Med

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Objective: Tributyltin (TBT) compounds have been widely used as antifouling agents for shipbottom paint. The immune system is a target of TBT intoxication. We evaluated the effects of TBT chloride in macrophages, which have critical roles in the immune system, using a murine macrophage lineage cell line, J774.1, in vitro.Methods: We examined tumor necrosis factor α (TNFα), interleukin-1β (IL-1β) and c-jun mRNA expression in J774.1 cells. The effects of TBT on the apoptosis of J774.1 cells were examined by determining the percentage of TUNEL-positive cells and caspase-3 activity.Results: The mean values of the viabilities of J774.1 cells exposed to TBT decreased dose-dependently. The relative mRNA expression of TNFα increased dose-dependently, however, that of IL-1β was not significantly different among the groups. The mean percentage of TUNEL-positive cells increased dose-dependently. Increases in the caspase-3 activities of J774.1 cells were observed in the groups exposed to higher concentrations of TBT. The mean value of relative mRNA expression of c-Jun transcription factor increased dose-dependently.Conclusions: The increases in the percentage of TUNEL-positive cells and in caspase-3 activity suggested that exposure to TBT induces apoptosis of J774.1 cells. The increases in the mRNA expression of TNFα and c-jun by TBT may be related to apoptosis in macrophages.

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Cytochrome c release and caspase activation in hydrogen peroxide‐ and tributyltin‐induced apoptosis

Cited by 245 publications

References 28 publications

Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug‐resistant colon carcinoma cells (LoVo) than on their wild‐type counterparts

Enzymatic oxidation products of spermine induce greater cytotoxic effects on human multidrug‐resistant colon carcinoma cells (LoVo) than on their wild‐type counterparts

Caspase activation in the absence of mitochondrial changes in granulocyte apoptosis

Tributyltin (TBT) increases TNFα mRNA expression and induces apoptosis in the murine macrophage cell line in vitro

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