Expression pattern of the bcl-2 homologous protein bad in normal skin, psoriasis vulgaris and keratinocytic tumors

Tomková, H.; Fujimoto, Wataru; Arata, Jirô

doi:10.1016/s0923-1811(99)00058-4

Cited by 31 publications

(38 citation statements)

References 21 publications

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“…In contrast to some studies with human tissues (Tomková et al, 1998;Batinac et al, 2007), but in agreement with others (Krajewski et al, 1994;Penault-Llorca et al, 1998), no gradient was observed for BAX in the canine epidermis. Similarly, no gradient was observed for Bak in the canine colon, skin, trachea, and prostate gland, in contrast to descriptions of some human studies (Krajewski et al, 1996;Tomková et al, 1998;Batinac et al, 2007;Duckworth and 2,4,5,6,7) and weak bands at 26 kDa (lanes 4, 5) and 23 kDa (lane 6) interpreted as BAX isoforms; polyclonal BAX-AbA20 weakly labels additional bands at 28, 40 and 70 kDa in some organs. Labelling with Bak-AbNT antibody variably shows two major bands at 24 kDa (corresponding to the expected size of Bak) and 70 kDa.…”

Section: Discussionsupporting

confidence: 90%

Immunohistochemical expression of Bax and Bak in canine non-neoplastic tissues

Croci

Dettwiler

Vaughan

et al. 2013

The Veterinary Journal

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Apoptosis is critical for embryonic development, maintenance of tissue homeostasis and protection against malignant transformation. The Bcl-2 family of proteins plays a key role in intrinsic apoptosis by controlling the integrity of the outer mitochondrial membrane, and the multidomain pro-apoptotic Bcl-2 family members Bax and Bak are essential components of this pathway. The aim of this study was to provide data on the expression of these proteins in normal canine tissues. Two antibodies against Bax recognising different conformations of the protein and one antibody against Bak were validated by immunohistochemistry and immunoblotting using canine recombinant proteins and keratinocytes treated with ultraviolet light. The antibodies were used immunohistochemically to label a wide panel of histologically normal tissues assembled on tissue microarrays. In addition, a subset of the tissues was evaluated by Western blot analysis. Immunohistochemical and Western blot analyses revealed that both Bax and Bak are widely expressed in non-neoplastic tissues from adult dogs. Immunohistochemistry showed almost exclusively cytoplasmic labelling and prominent labelling of epithelial cells. In lymph nodes, immunohistochemical labelling was diffuse for both proteins and showed enhanced intensities in the mantle zones for Bax and the germinal centres for Bak. Strong reactivity for the active conformation of Bax was detected only in enterocytes and Leydig cells and in scattered lymphocytes. These data indicate widespread expression of Bax and Bak in normal canine tissues. Knowledge of the expression of Bax and Bak in normal tissues is a prerequisite in assessing the role of these proteins in canine neoplastic disease. AbstractApoptosis is critical for embryonic development, maintenance of tissue homeostasis and protection against malignant transformation. The Bcl-2 family of proteins plays a key role in intrinsic apoptosis by controlling the integrity of the outer mitochondrial membrane, and the multidomain pro-apoptotic Bcl-2 family members Bax and Bak are essential components of this pathway. The aim of this study was to provide data on the expression of these proteins in normal canine tissues. Two antibodies against Bax recognising different conformations of the protein and one antibody against Bak were validated by immunohistochemistry and immunoblotting using canine recombinant proteins and keratinocytes treated with ultraviolet light. The antibodies were used immunohistochemically to label a wide panel of histologically normal tissues assembled on tissue microarrays. In addition, a subset of the tissues was evaluated by Western blot analysis. Immunohistochemical and Western blot analyses revealed that both Bax and Bak are widely expressed in non-neoplastic tissues from adult dogs. Immunohistochemistry showed almost exclusively cytoplasmic labelling and prominent labelling of epithelial cells. In lymph nodes, immunohistochemical labelling was diffuse for both proteins and showed enhanced intensities in the mantl...

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Section: Discussionsupporting

confidence: 90%

Immunohistochemical expression of Bax and Bak in canine non-neoplastic tissues

Croci

Dettwiler

Vaughan

et al. 2013

The Veterinary Journal

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“…These data seem to suggest that Bax protein does not play any part in the apoptosis of keratinocytes either in EM or in SJS/TEN. On the other hand, other authors found Bax immunoreactivity in normal epidermis and its appendages (31). These results are discrepant with our finding of negative Bax and Bel-2 stainings in normal epidermis.…”

Section: Pi: Steven-johnson Syndrome (Sjs) Versus Healthy Skin (Hs) Pcontrasting

confidence: 99%

Immunohistochemical Expression of Apoptotic Markers in Drug-Induced Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Marzano

Frezzolini

Caproni

et al. 2007

Int J Immunopathol Pharmacol

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Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are considered to be severity variants of the same disease, which is almost always associated with drug intake. In contrast, erythema multiforme (EM) is a disorder regarded as only rarely caused by drugs. Keratinocyte apoptosis has been shown to play an important part in the pathogenesis of SJS and TEN, whilst its role in EM remains controversial. To determine the expression of apoptosis-associated molecules Fas, Fas ligand (FasL), BcI-2 and Bax in the above disorders, an immunohistochemical anatysis was performed. We studied both lesional skin from thirty patients having drug-induced EM and 5 cases classified within the SJS/TEN spectrum and normal skin samples. We found a keratinocyte overexpression of Fas antigen, an important molecule mediating apoptosis, not only in SJS and TEN but also in EM. Another noteworthy finding was the strong expression of BcI-2, a protein known as blocking apoptosis, along the basal layer and in the dermal infiltrate both in SJS/TEN and in EM. Taken together, these findings suggest that Fas-dependent keratinocyte apoptosis may playa part in the pathogenesis of both SJS/TEN and EM. Fas-mediated cell death may be partially suppressed by the BcI-2 protein.Until recently, most textbooks of medicine considered erythema multi forme (EM) to be a spectrum of disorders that included EM majus, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). A few years ago, some authors suggested that EM majus is different from SJS and TEN, not only in severity but also in the pattern and distribution of the skin lesions, whereas SJS and TEN are only severity variants of a single entity (1-4).This last is almost always associated with drug intake, whilst EM, both in its majus variant and in the form so-called minor, is predominantly caused by preceding infections, notably with herpes simplex virus (HSV), and only rarely by drugs.

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“…Wyniki dotychczasowych badań nad rolą tych białek w łuszczycy są niejednoznaczne. Część autorów wykazało znacząco mniejszą ekspresję Bcl-2 oraz większą ekspresję Bcl--xL i Bax w naskórku pacjentów z łuszczycą [11,16]. Inni nie obserwowali istotnych różnic w ekspresji Bcl-2 w naskórku i w stężeniu Bcl-2 w surowicy pacjentów z łuszczycą w porównaniu z osobami zdrowymi [17,18].…”

Section: Apoptoza W łUszczycyunclassified

“…O słuszności tej koncepcji świadczą wyniki badań uzyskane przez Tomkovą i wsp. [16]. Autorzy tej pracy obok widocznej ekspresji proapoptotycznego białka Bax w naskórku łuszczycowym stwierdzili jednocześnie znacząco większą ekspresję antyapoptotycznego białka Bcl-xL.…”

Section: Apoptoza W łUszczycyunclassified

Selected aspects of apoptosis in psoriasis

Myśliwiec¹,

Baran²,

Flisiak³

2017

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StreSzczenIeApoptoza jest procesem fizjologicznej, programowanej śmierci komó-rek, która w odróżnieniu od nekrozy nie powoduje stanu zapalnego. Ma podstawowe znaczenie dla funkcjonowania różnych tkanek i narządów. Równowaga pomiędzy proliferacją a apoptozą keratynocytów jest istotna dla prawidłowej homeostazy naskórka. W schorzeniach skóry może dochodzić do pobudzenia apoptozy, co prowadzi zazwyczaj do chorób o ostrym przebiegu, lub jej zahamowania, co skutkuje częściej rozwojem chorób przewlekłych. Łuszczyca jest przewlekłą chorobą zapalną charakteryzującą się nadmierną proliferacją oraz zaburzeniem różnicowania keratynocytów. Keratynocyty łuszczycowe mają zmniejszoną zdolność do apoptozy, co może mieć duże znaczenie dla przerostu naskórka w łuszczycy. Zaburzenia apoptozy w łuszczycy dotyczą również komórek układu immunologicznego. W pracy omó-wiono podstawy procesu apoptozy, a także jej wybrane aspekty w patogenezie łuszczycy. ABStrActApoptosis is a physiological mechanism of programmed cell death, in contrast to necrosis, without eliciting an inflammatory response. It plays the key role in the functioning of different tissues and organs. The balance between proliferation and apoptosis of keratinocytes is important for epidermal maintenance of homeostasis. Dysfunctional apoptosis plays an important role in the development of several skin disorders. Diseases with an increase of apoptosis are usually acute, while those with inhibited apoptosis tend to be chronic. Psoriasis is an immune-mediated chronic inflammatory skin disease. It is characterized by keratinocyte hyperproliferation and abnormal differentiation. Psoriatic keratinocytes are resistant to apoptosis and this phenomenon can be the key event in psoriatic hyperplasia. Apoptosis disturbances can also affect immune cells involved in the pathogenesis of psoriasis. In this review, we describe the basic concept of apoptosis and its relevance in psoriatic pathogenesis.

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Expression pattern of the bcl-2 homologous protein bad in normal skin, psoriasis vulgaris and keratinocytic tumors

Cited by 31 publications

References 21 publications

Immunohistochemical expression of Bax and Bak in canine non-neoplastic tissues

Immunohistochemical expression of Bax and Bak in canine non-neoplastic tissues

Immunohistochemical Expression of Apoptotic Markers in Drug-Induced Erythema Multiforme, Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

Selected aspects of apoptosis in psoriasis

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