Fas Antigen Modulates Ultraviolet B-Induced Apoptosis of SVHK Cells: Sequential Activation of Caspases 8, 3, and 1 in the Apoptotic Process

Takahashi, Hidetoshi; Nakamura, Satoshi; Asano, Katsuaki; Kinouchi, Motoshi; Ishida‐Yamamoto, Akemi; Iizuka, Hajime

doi:10.1006/excr.1999.4476

Cited by 58 publications

(75 citation statements)

References 38 publications

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“…These observations suggest that a caspase-3-like protease is a major component of the cellular machinery leading to UVB-induced cell death. Participation of the caspase-3-like protease in UVBinduced cell death had been demonstrated previously (36,37). Our data indicate that selenite treatment suppresses both cell death and DNA fragmentation induced by UVB radiation.…”

Section: Discussionsupporting

confidence: 85%

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Selenite Negatively Regulates Caspase-3 through a Redox Mechanism

Park

Huh

Kim

et al. 2000

Journal of Biological Chemistry

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Selenium, an essential biological trace element, exerts its modulatory effects in a variety of cellular events including cell survival and death. In our study we observed that selenite protects HEK293 cells from cell death induced by ultraviolet B radiation (UVB). Exposure of HEK293 cells to UVB radiation resulted in the activation of caspase-3-like protease activity, and pretreatment of the cells with z-DEVD-fmk (N-benzyloxycarbonyl-Asp-Glu-Val-Asp-fluoromethylketone), a caspase-3 inhibitor, prevented UVB-induced cell death. Interestingly, enzymatic activity of caspase-3-like protease in cell lysates of UVB-exposed cells was repressed in vitro by the presence of selenite. Selenite also inhibited the in vitro activity of purified recombinant caspase-3 in cleaving Ac-DEVD-pNA (N-acetyl-Asp-Glu-Asp-p-nitroanilide) or ICAD L (inhibitor of a caspase-activated deoxyribonuclease) and in the induction of DNA fragmentation. The inhibitory action of selenite on a recombinant active caspase-3 could be reversed by sulfhydryl reducing agents, such as dithiothreitol and ␤-mercaptoethanol. Furthermore, pretreatment of cells with selenite suppressed the stimulation of the caspase-3-like protease activity in UVB-exposed cells, whereas dithiothreitol and ␤-mercaptoethanol reversed this suppression of the enzymatic activity. Taken together, our data suggest that selenite inhibits caspase-3-like protease activity through a redox mechanism and that inhibition of caspase-3-like protease activity may be the mechanism by which selenite exerts its protective effect against UVB-induced cell death.Selenium, an essential trace element in the biological system, has been shown to modulate the functions of a variety of intracellular proteins (1-4). Selenium exerts many of its functions by being incorporated into the proteins as selenocysteine or selenomethionine (5-7). The selenoproteins include glutathione peroxidases, formate dehydrogenases, and glycine reductases (5). Selenium can also regulate the functions of many proteins through the oxidation of reactive cysteine residues in the proteins (1-3, 8). Those proteins that can be regulated by selenium through a redox mechanism include Na,K-ATPase, a glucocorticoid receptor, prostaglandin synthase, nuclear factor B and the transcription factor adaptor protein-1 (1-3, 9 -11). Thus, selenium appears to regulate functions of various proteins, many of which are associated with intracellular signal transmission in diverse cellular events (3, 12, 13). There are many lines of evidence pointing to selenite and other selenium compounds as playing critical roles in the protection of cells against cell death initiated by various stresses such as ultraviolet (UV) 1 and ionizing irradiation (14 -17). A regulatory mechanism for the anti-death effect of selenite and other selenium compounds, however, remains to be found.Apoptosis is a cell suicide process with characteristic morphological features that include nuclear membrane breakdown, chromatin condensation and fragmentation, cell membrane blebbing, and...

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Section: Discussionsupporting

confidence: 85%

“…Protease Activity-Exposure of cells to UVB has been shown to induce activation of the proapoptotic proteins including caspases (35)(36)(37). Indeed, the enzymatic activity of a caspase-3-like protease was markedly enhanced after HEK293 cells had been exposed to UVB (Fig.…”

Section: Uvb-induced Cell Death Is Dependent Upon Caspase-3-likementioning

confidence: 99%

Selenite Negatively Regulates Caspase-3 through a Redox Mechanism

Park

Huh

Kim

et al. 2000

Journal of Biological Chemistry

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“…13,14 In line with this proposed mechanism, studies in mice with mutated FasL suggested that upregulation of Fas and FasL expression after irradiation with high doses of UVB contribute to apoptosis of epidermal keratinocytes. 15 However, UVBinduced keratinocyte apoptosis has also been described to proceed through the internal, mitochondrial pathway.…”

mentioning

confidence: 88%

Enhanced contact allergen- and UVB-induced keratinocyte apoptosis in the absence of CD95/Fas/Apo-1

et al. 2010

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FAS/CD95/Apo-1 is a ubiquitously expressed cell-surface receptor involved in the initiation of programmed cell death. Its function in epidermal keratinocytes has been incompletely defined. Available evidence from in vitro studies points to important roles of Fas in the pathogenesis of contact dermatitis and in keratinocyte apoptosis induced by ultraviolet light. To define functions of Fas in the epidermis in vivo, we have generated mice with epidermis-specific deletion of the fas gene and tested its requirement for 2,4-dinitrofluorobenzene-induced contact dermatitis and for ultraviolet light B (UVB)-induced keratinocyte apoptosis. We report here our unexpected finding that keratinocyte apoptosis induced by both a contact allergen and UVB irradiation was significantly enhanced in Fas-negative epidermis. Expression of Fas by epidermal keratinocytes was neither necessary for the normal development of contact hypersensitivity of the skin, nor required for keratinocyte apoptosis following UVB irradiation. Our study results thus show that in the epidermis in vivo Fas exerts antiapoptotic effects that outweigh its proapoptotic role in contact hypersensitivity responses of the skin and in the tissue response of the epidermis to UVB irradiation.

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“…The oligomerization of Apaf-1 promotes the allosteric activation of caspase 9 by forming the Apaf-1 apoptosome [117]. Caspase 9 can subsequently activate caspase 3 [117] as well as caspase 1 through the intermediary caspase 8 [212]. Together, caspase 1 and caspase 3 lead to both DNA fragmentation and membrane PS exposure [38,117,139].…”

Section: Induction Of Intrinsic and Extrinsic Caspase Pathways For Cementioning

confidence: 99%

Stress in the brain: novel cellular mechanisms of injury linked to Alzheimer's disease

Chong

Maiese

2005

Brain Research Reviews

135

121

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More than a century has elapsed since the description of Alois Alzheimer's patient Auguste D. Yet, the well-documented generation of β-amyloid aggregates and neurofibrillary tangles that define Alzheimer's disease is believed to represent only a portion of the cellular processes that can determine the course of Alzheimer's disease. Understanding of the complex nature of this disorder has evolved with an increased appreciation for pathways that involve the generation of reactive oxygen species and oxidative stress, apoptotic injury that leads to nuclear degradation in both neuronal and vascular populations, and the early loss of cellular membrane asymmetry that mitigates inflammation and vascular occlusion. Recent work has identified novel pathways, such as the Wnt pathway and the serine-threonine kinase Akt, as central modulators that oversee cellular apoptosis and the formation of neurofibrillary tangles through their downstream substrates that include glycogen synthase kinase-3β, Bad, and Bcl-x L . Other closely integrated pathways control microglial activation, release of inflammatory cytokines, and caspase and calpain activation for the processing of amyloid precursor protein, tau protein cleavage, and presenilin disposal. New therapeutic avenues that are just open to exploration, such as with nicotinamide adenine dinucleotide modulation, cell cycle modulation, metabotropic glutamate system modulation, and erythropoietin targeted expression, may provide both attractive and viable alternatives to treat Alzheimer's disease.

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Fas Antigen Modulates Ultraviolet B-Induced Apoptosis of SVHK Cells: Sequential Activation of Caspases 8, 3, and 1 in the Apoptotic Process

Cited by 58 publications

References 38 publications

Selenite Negatively Regulates Caspase-3 through a Redox Mechanism

Selenite Negatively Regulates Caspase-3 through a Redox Mechanism

Enhanced contact allergen- and UVB-induced keratinocyte apoptosis in the absence of CD95/Fas/Apo-1

Stress in the brain: novel cellular mechanisms of injury linked to Alzheimer's disease

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