Death penalty for keratinocytes: apoptosis versus cornification

Lippens, Saskia; Denecker, Geertrui; Ovaere, Petra; Vandenabeele, Peter; Declercq, Wim

doi:10.1038/sj.cdd.4401722

Cited by 199 publications

(181 citation statements)

References 120 publications

(159 reference statements)

Supporting

Mentioning

173

Contrasting

Unclassified

Order By: Relevance

“…The physiology of keratinocytes involves two important pathways of proliferation and differentiation for epidermis repair [17]. However, our results did not determine whether remifentanil treatment confers positive effect on differentiation in human keratinocytes.…”

Section: Discussioncontrasting

confidence: 53%

The Effect of Remifentanil Preconditioning on Injured Keratinocyte

Hong

Kim

Yoon

et al. 2014

J Korean Dent Soc Anesthesiol

View full text Add to dashboard Cite

Background: Incisional site of surgical operation become transient ischemic state and then occur reoxygenation due to vasodilatation by inflammatory reaction, the productive reactive oxygen species (ROS) give rise to many physiologic results. Apoptosis have major role on elimination of inflammatory cell and formation of granulation tissue in normal wound healing process. Remifentanil can prevent the inflammatory response and can suppress inducible nitric oxide synthase expression in a septic mouse model. After cardiopulmonary bypass for coronary artery surgery, remifentanil can also inhibit the release of biomarkers of myocardial damage. Here we investigated whether remifentanil pretreatment has cellular protective effect against hypoxia-reoxygenation in HaCaT human keratinocytes, if so, the role of apoptosis and autophagy on this phenomenon. Methods: The HaCaT human keratinocytes were exposed to various concentrations of remifentanil (0.01, 0.05, 0.1, 0.5 and 1 ng/ml) for 2 h before hypoxia (RPC/HR group). These cells were cultured under 1% oxygen tension for 24h at 37°C. After hypoxia, to simulate reoxygenation and recovery, the cells were reoxygenated for 12 h at 37°C. 3-MA/RPC/HR group was treated 3-methyladenine (3-MA), autophagy inhibitor for 1h before remifentanil treatment. Cell viability was measured using a quantitative colorimetric assay with thiazolyl blue tetrazoliumbromide (MTT, amresco), showing the mitochondrial activity of living cells. To investigate whether the occurrence of autophagy and apoptosis, we used fluorescence microscopy and Western blot analysis. Results: The viability against hypoxia-reoxygenation injury in remifentanil preconditioning keratinocytes were increased, and these cells were showed stimulated expression of autophagy 3-MA suppressed the induction of autophagy effectively and the protective effects on apoptosis. Atg5, Beclin-1, LC3-II and p62 were elevated in RPC/HR group. But they were decreased when autophagy was suppressed by 3-MA. Conclusions: Remifentanil preconditioning showed the protective effect in human keratinocytes, and we concluded that autophagy may take the major role in the recovery of wound from hypoxia-reoxygenation injury. We suggest that further research is needed about the cell protective effects of autophagy.

show abstract

Section: Discussioncontrasting

confidence: 53%

The Effect of Remifentanil Preconditioning on Injured Keratinocyte

Hong

Kim

Yoon

et al. 2014

J Korean Dent Soc Anesthesiol

View full text Add to dashboard Cite

show abstract

“…The late stages of apoptosis that result in the distinctive morphology of an apoptotic cell are thought to occur rapidly, followed by phagocytic removal of the apoptotic bodies by neighbouring cells. Thus, an AI around 1% is interpreted as a significant amount of cell death (Darzynkiewicz et al, 1997;Lippens et al, 2005). Figure 2A compares the apoptotic indices of OSCC with low and high Pidd expression.…”

Section: Resultsmentioning

confidence: 99%

The expression of p53-induced protein with death domain (Pidd) and apoptosis in oral squamous cell carcinoma

et al. 2007

View full text Add to dashboard Cite

The Pidd (p53-induced protein with death domain) gene was shown to be induced by the tumour suppressor p53 and to mediate p53-dependent apoptosis in mouse and human cells, through interactions with components of both the mitochondrial and the death receptor signalling pathways. To study the role of Pidd in clinical tumours, we measured its expression by quantitative reverse transcription-PCR in microdissected oral squamous cell carcinomas (OSCC) with and without p53 mutation. Tumour cell apoptosis was assessed by in situ terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling. Tumour proliferation was assessed by immunohistochemical staining for the Ki-67 antigen. We found a wide range of Pidd expression among OSCC. Statistical analysis revealed an association between Pidd expression and apoptotic index (Mann -Whitney test, Po0.001), consistent with a role of Pidd in apoptosis in this tumour type. Furthermore, we showed a positive correlation between apoptotic index and proliferative index that has not been previously described for OSCC. There was no correlation between Pidd expression and the p53 mutation status of these tumours, suggesting that Pidd expression may be regulated by p53-independent mechanisms. Further characterisation of these molecular defects in the control of proliferation and apoptosis should help in developing treatments that target OSCC according to their biological properties.

show abstract

“…Although keratinocytes from the lower strata undergo apoptosis in response to UV-induced DNA damage, such a response in granular layer keratinocytes needed for stratum corneum assembly would be catastrophic, leaving underlying cells without protection (39). In addition, it may not be necessary to remove cells harboring UV-induced DNA damage if they are soon to be "cornified" and shed into the environment.…”

Section: Discussionmentioning

confidence: 99%

AKT-dependent HspB1 (Hsp27) Activity in Epidermal Differentiation

O'Shaughnessy

Welti

Cooke

et al. 2007

Journal of Biological Chemistry

117

View full text Add to dashboard Cite

AKT activity has been reported in the epidermis associated with keratinocyte survival and differentiation. We show in developing skin that Akt activity associates first with post-proliferative, para-basal keratinocytes and later with terminally differentiated keratinocytes that are forming the fetal stratum corneum. In adult epidermis the dominant Akt activity is in these highly differentiated granular keratinocytes, involved in stratum corneum assembly. Stratum corneum is crucial for protective barrier activity, and its formation involves complex and poorly understood processes such as nuclear dissolution, keratin filament aggregation, and assembly of a multiprotein cell cornified envelope. A key protein in these processes is filaggrin. We show that one target of Akt in granular keratinocytes is HspB1 (heat shock protein 27). Loss of epidermal HspB1 caused hyperkeratinization and misprocessing of filaggrin. Akt-mediated HspB1 phosphorylation promotes a transient interaction with filaggrin and intracellular redistribution of HspB1. This is the first demonstration of a specific interaction between HspB1 and a stratum corneum protein and indicates that HspB1 has chaperone activity during stratum corneum formation. This work demonstrates a new role for Akt in epidermis.The epidermis is the primary environmental barrier, protecting from infection, allergens, and damage from UV radiation. The major constituent of this epidermal barrier is the terminally differentiated, anuclear keratinocyte. This structure is bounded by a cornified envelope, an elaborate, cross-linked protein structure covalently bound to hydrophobic lipid externally and aggregated keratin internally (1). Formation of this structure is poorly understood.The complexity of keratinocyte terminal differentiation and the importance of precisely timed and compartmentalized processing is illustrated by the maturation of the stratum corneum protein filaggrin. Filaggrin is synthesized as a high molecular mass precursor comprising multiple subunits that are sequentially processed and modified in temporally and spatially regulated steps by diverse proteases and enzymes to produce mature filaggrin subunits. Mature filaggrin is thought to be important in the aggregation and collapse of the keratin network leading to flattening of the keratinocyte and the destruction of the nucleus in granular layer (terminally differentiating) keratinocytes (2). Filaggrin is also incorporated into the cornified envelope (2). Premature or aberrant filaggrin processing can be catastrophic, leading to disruption of cornified envelope integrity and skin barrier function (3-5) and is far more damaging than reduced filaggrin levels that, in contrast, lead only to mild skin defects (6).Possible regulators of protein processing and trafficking during terminal differentiation are heat shock proteins (Hsps). 2Hsps have diverse roles as cellular chaperones, anti-apoptotic factors, stress-protective proteins, and cytoskeletal stabilizers (7,8). Human HspB1 (Hsp27) (9 -11) and the mouse HspB1...

show abstract

Death penalty for keratinocytes: apoptosis versus cornification

Cited by 199 publications

References 120 publications

The Effect of Remifentanil Preconditioning on Injured Keratinocyte

The Effect of Remifentanil Preconditioning on Injured Keratinocyte

The expression of p53-induced protein with death domain (Pidd) and apoptosis in oral squamous cell carcinoma

AKT-dependent HspB1 (Hsp27) Activity in Epidermal Differentiation

Contact Info

Product

Resources

About