Cyclosporine A enhances apoptosis in gingival keratinocytes of rats and in OECM1 cells via the mitochondrial pathway

Tu, Hsiao-Pei; Chen, Y.-T.; Chiu, Hsien‐Chung; Chin, Yu Tang; Huang, Shih‐Ming; Cheng, Linyou; Fu, Earl; Chiang, Cheng‐Yang

doi:10.1111/j.1600-0765.2008.01189.x

Cited by 15 publications

(15 citation statements)

References 48 publications

(64 reference statements)

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“…Taking together these previous and present results, it is reasonable to suggest that both the extrinsic and intrinsic pathways might have been involved in the cyclic stretch-induced apoptosis in PDL cells, but functioned differently in the apoptosis induced by 6 and 24 h stretches respectively. As to in vivo situation, Tu et al and Leone et al reported the results of immunohistochemistry analysis suggesting the presence of caspase-9 in gingivae from SD rats and from human tissue, respectively [27, 28]. With respect to caspase-8, though there were no published studies showing in situ labelling for caspase-8 in periodontal tissue, the caspase-8 immunohistochemically positive fibroblast-like cells have been observed in human implant interface membrane [29].…”

Section: Discussionmentioning

confidence: 99%

Caspase-8 and Caspase-9 Functioned Differently at Different Stages of the Cyclic Stretch-Induced Apoptosis in Human Periodontal Ligament Cells

Zhao

Zhuang

et al. 2016

PLoS ONE

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BackgroundHuman periodontal ligament (PDL) cells underwent apoptosis after mechanical stretch loading. However, the exact signalling pathway remains unknown. This study aimed to elucidate how the apoptotic caspases functioned in the cyclic stretch-induced apoptosis in human PDL cells.Materials and MethodsIn the present study, 20% cyclic stretch was selected to load the cells for 6 or 24 h. The following parameters were analyzed: apoptotic rates, the protein levels of caspase-3, -7, -8 and -9 and the activities of caspase-8 and -9. Subsequently, the influences of caspase-8 and caspase-9 inhibitors on the apoptotic rate and the protein level of the activated caspase-3 were assessed as well.ResultsThe apoptotic rates increased in response to cyclic stretch, but the cells entered different apoptotic stages after 6 and 24 h stretches. Caspase-3, -7, -8 and -9 were all activated after stretch loading. The stretch-induced apoptosis and the protein level of the activated caspase-3 were inhibited after inhibiting both caspase-8 and caspase-9 in both 6 and 24 h stretched cells and after inhibiting caspase-9 in 24 h stretched cells.ConclusionCaspase-8 and -9 functioned differently at different apoptotic stages in human PDL cells after cyclic stretch.

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Section: Discussionmentioning

confidence: 99%

Caspase-8 and Caspase-9 Functioned Differently at Different Stages of the Cyclic Stretch-Induced Apoptosis in Human Periodontal Ligament Cells

Zhao

Zhuang

et al. 2016

PLoS ONE

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“…Hydrogen sulphide, a main cause of physiologic halitosis, seems to induce apoptosis in human gingival by mitochondrial pathway 19 . Cyclosporine A might enhance the apoptosis of gingival keratinocytes, mainly by the mitochondrial pathway 20 . Apoptosis is frequently found in lichen planus.…”

Section: Discussionmentioning

confidence: 99%

“…19 Cyclosporine A might enhance the apoptosis of gingival keratinocytes, mainly by the mitochondrial pathway. 20 Apoptosis is frequently found in lichen planus. The high frequency of intrinsic apoptotic pathway markers caspase-2 and caspase-12 indicates intracellular stress in atrophic oral lichen planus epithelial cells.…”

mentioning

confidence: 99%

Caspase‐3/caspase‐8, bax and bcl2 in pulps of human primary teeth with physiological root resorption

Rodrigues

Puerto

Brant

et al. 2011

Int J Paed Dentistry

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OBJECTIVE. Physiological root resorption is a programmed event that takes place in primary teeth leading to elimination of all root structures. The mechanism behind pulp elimination indicates apoptosis, but its pathway has not been well characterised yet. To better understand this event, we evaluated the gene expression of bax, bcl-2, caspase-3 and caspase-8 through real-time polymerase chain reaction (PCR) and immunohistochemistry expression of Caspase-8 and Bax in pulps. METHODS. Samples were split into two groups: pulps from primary teeth with physiological root resorption (n = 40) and control (n =40), pulps from permanent teeth. Samples of each group were split into PCR (n = 20) and immunohistochemistry (n = 20). RESULTS. Pulps from primary teeth showed a higher caspase-3 mRNA level than pulps from permanent teeth. The expression of bax gene was more intense than caspase-8 but both did not show difference between groups. The bcl-2 mRNA level was incipient and similar between groups. Histopath slides did not show any evidence of inflammatory infiltration, which implies that extrinsic via is not likely to be involved. Immunohistochemistry reaction to Bax and Caspase-8 supported PCR results. CONCLUSIONS. Pulp apoptosis is likely to occur via caspase-3 activation through the mitochondrial pathway.

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“…35,36 In this procedure, internucleosomal DNA fragmentation is quantitatively According to the protocol described by Liu et al 35 and Tu et al 36 , cells were centrifuged (200 g), resuspended in 200 µL of the lysis buffer supplied in the kit and incubated for 30 min at room temperature. Nuclei were then pelleted at 200 g for 10 min and 20 µL of the supernatant (cytoplasmic fraction) from the treated group, untreated group, positive control and background control were transferred into the corresponding streptavidincoated wells for the enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's standard protocol.…”

Section: Cell Death Detectionmentioning

confidence: 99%

“…Nuclei were then pelleted at 200 g for 10 min and 20 µL of the supernatant (cytoplasmic fraction) from the treated group, untreated group, positive control and background control were transferred into the corresponding streptavidincoated wells for the enzyme-linked immunosorbent assay (ELISA) according to the manufacturer's standard protocol. 36 Then, 80 µL of the immunoreagent was added to each well containing the 20 µL supernatant or controls. The wells were covered with adhesive foil and incubated on a microplate shaker under gentle shaking (300 rpm) for 2 h at room temperature.…”

Section: Cell Death Detectionmentioning

confidence: 99%

In-vitro effects of protease inhibitors on BAX, BCL-2 and apoptosis in two human breast cell lines (with corrigendum)

2015

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Currently, the treatment of choice of HIV/AIDS in South Africa is the multidrug combination regimen known as HAART (highly active antiretroviral treatment). HAART, which commonly consists of nucleoside or non-nucleoside reverse transcriptase inhibitors and protease inhibitors, has radically decreased mortality and morbidity rates among people living with HIV/AIDS. The emphasis of the original development of the antiretroviral drugs was on clinical effectiveness (reducing mortality). Presently, emphasis has shifted from the initial short- term considerations to the long-term undesirable or harmful effects induced by this treatment regimen. Whether antiretroviral compounds are oncogenic is widely speculated, which led to this investigation into the effects of protease inhibitors on the expression of key apoptotic regulatory genes, BAX and BCL-2, in two human breast cell lines, MCF-7 and MCF-10A by real-time qPCR gene expression and immunofluorescence. The anti-apoptotic effects of the protease inhibitors – LPV/r were also investigated by cell death detection ELISA and acridine orange staining. This study also evaluated the cytotoxicity of the antiretroviral drugs in normal and cancer cell lines of the breast (at clinically relevant concentrations of the drugs and at different time points, 24–96 h), employing the neutral red uptake assay. The drugs and combinations tested did not alter BAX and BCL-2 gene expression and protein expression and localisation in both cell lines. In addition, the protease inhibitors–LPV/r did not inhibit camptothecin-induced apoptosis in both cell lines. We have shown that the protease inhibitors demonstrated varying degrees of cytotoxicity in the breast cells. The resulting DNA damage associated with cytotoxicity is strongly implicated in the processes of tumour initiation.

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Cyclosporine A enhances apoptosis in gingival keratinocytes of rats and in OECM1 cells via the mitochondrial pathway

Abstract: Based on the above findings, we suggest that cyclosporine A might enhance the apoptosis of gingival keratinocytes, mainly via the mitochondrial pathway.

Cited by 15 publications

References 48 publications

Caspase-8 and Caspase-9 Functioned Differently at Different Stages of the Cyclic Stretch-Induced Apoptosis in Human Periodontal Ligament Cells

Caspase-8 and Caspase-9 Functioned Differently at Different Stages of the Cyclic Stretch-Induced Apoptosis in Human Periodontal Ligament Cells

Caspase‐3/caspase‐8, bax and bcl2 in pulps of human primary teeth with physiological root resorption

In-vitro effects of protease inhibitors on BAX, BCL-2 and apoptosis in two human breast cell lines (with corrigendum)

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