Apoptosis in Thyroid Tissue from Patients with Hashimoto's Thyroiditis

Kotani, Takuya; Aratake, Yatsuki; Hirai, Keisuke; Fukazawa, Yuichirou; Sato, Haru–Tada; Ohtaki, Sachiya

doi:10.3109/08916939508995700

Cited by 100 publications

(78 citation statements)

References 10 publications

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“…Flow cytometric analysis showed more clearly that ceramide induced apoptotic cell death in FRTL-5 thyroid cells. Recently, several studies demonstrated that apoptosis was involved in cell death of normal thyrocyte and thyroid diseases such as goiter (Tamura et al, 1998) and thyroiditis (Kotani et al, 1995), and also suggested that the mechanisms by which thyroid cells undergo apoptosis were mediated by Fas/Fas ligand system (Arscott et al, 1997;Tamura et al, 1998). In consideration of several findings indicating that sphingomyelin pathway is involved in Fasmediated apoptotic signaling in various type of cells (Gulbins et al, 1995;Tepper et al, 1997;Boesen-de Cock et al, 1998), our results also suggested that ceramide may play a role in Fas-mediated apoptosis in thyroid cells.…”

Section: Discussionmentioning

confidence: 99%

“…However, to our knowledge, no reports have been available about ceramide-induced apoptosis and effect of ceramide on PLD activity in thyroid cell. In thyroid cells, apoptosis is suspected of being involved in the regulation of normal glandular size and appears to be one of the major modes of thyrocyte death in autoimmune thyroid disease (Kotani et al, 1995;Tanimoto et al, 1995). With these premises, in the present study we have examined the effects of ceramide on apoptotic cell death and the possibility that PLD may be involved in apoptotic cell death in FRTL-5 thyroid cells.…”

Section: Introductionmentioning

confidence: 99%

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Effect of ceramide on apoptosis and phospholipase D activity in FRTL-5 thyroid cells

Park¹,

Kim²,

Han³

et al. 1999

Exp Mol Med

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Ceramide, a product of sphingomyelin hydrolysis, is now recognized as an intracellular lipid messenger, which mediates the effects of extracellular agents on cellular growth, differentiation and apoptosis. Recently, ceramide has been implicated in the regulation of phospholipase D (PLD). In this study, we examined the effects of ceramide on the activity and mRNA level of PLD during apoptotic process in FRTL-5 thyroid cells. C 2 -ceramide (N-acetyl sphingosine) induced apoptosis in FRTL-5 thyroid cells. Fluorescent staining showed that ceramide induced the typical features of apoptosis including condensed or fragmented nuclei. DNA fragmentation was also observed by agarose gel electrophoresis. Flow cytometric cell cycle analysis showed more clearly that ceramide induced apoptotic cell death in FRTL-5 thyroid cells. The treatment of FRTL-5 thyroid cells with thyroid-stimulating hormone (TSH) resulted in an increased PLD activity in a dose-and time-dependent manner. However, the TSH-induced increase in PLD activity was down-regulated within 2 h after ceramide treatment. Furthermore, the levels of PLD mRNA were found to be decreased throughout apoptotic process as inferred by reverse transcription-polymerase chain reaction. However, the decreases in PLD mRNA levels were not correlated with those in PLD activities after ceramide treatment. Taken together, these data suggest that ceramide inhibits the PLD activity in an early apoptotic phase and down-regulation of the levels of PLD mRNA may be implicated in apoptotic process in FRTL-5 thyroid cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of ceramide on apoptosis and phospholipase D activity in FRTL-5 thyroid cells

Park¹,

Kim²,

Han³

et al. 1999

Exp Mol Med

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“…HT is characterized primarily by destruction of thyroid tissue. Immunohistological investigation of HT tissue indicates that apoptosis might be a possible mechanism for cell death of thyrocytes (1,2), whereas reduced thyrocyte cell death was observed in the stimulated thyroids from GD patients (2).…”

Section: Introductionmentioning

confidence: 97%

Fas and Fas ligand gene expression in autoimmune thyroiditis in BB/W rats

Blüher

Krohn²,

Wallaschofski³

et al. 1999

European Journal of Endocrinology

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Objective: Apoptosis via the Fas pathway is a potential mechanism for thyroid tissue destruction leading to clinical hypothyroidism in Hashimoto's thyroiditis (HT). Recent studies reported contradictory results regarding the regulation of Fas/Fas ligand (FasL) expression by cytokines in vitro. We therefore determined the Fas and FasL gene expression in the BioBreeding/Worcester (BB/W) rat thyroiditis model, which can be regarded as a model for HT. Methods: In order to obtain BB/W rats with spontaneous, iodine-induced or without lymphocytic thyroiditis (LT), rats were divided into 3 groups: 55-day-old rats after 24 days of iodine administration, 75-day-old rats after 45 days of iodine administration, and 101-day-old rats respectively. The gene expression of Fas, FasL, and interleukin (IL)-1b was determined by Genescan fragment analysis using reverse polymerase chain reaction. Serum thyroglobulin (TG) antibody concentrations were measured and the extent of lymphocytic infiltration of one thyroid lobe was histologically graded. Results: Fas and FasL gene expression was significantly higher in rats with LT and correlated with the extent of lymphocytic infiltration and the TG antibody level. There was no evidence that the expression of IL-1b or other cytokines is related to the expression of Fas or its ligand. Conclusions:The increased expression of Fas and FasL in LT of BB/W rats suggests the involvement of the Fas pathway in the pathogenesis of LT in BB/W rats. However, in contrast to results of recent in vitro studies, in the BB/W rat Fas/FasL expression is not regulated by IL-2, -4, -6, -10, -12, interferon g, and tumor necrosis factor a.

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“…Não há relatos na literatura sobre os índices apoptóticos em tiróides normais. Porém, sabe-se que a apoptose tem sido observada, ocasionalmente, em secções histológicas de tiróide normal (16), e este processo é anormalmente acelerado durante as fases de maior atividade da Tiroidite de Hashimoto (17).…”

Section: Discussionunclassified

Apoptose em tiroidopatias hiperplásias e neoplásicas

Lima

Rios

Oliveira

et al. 2000

Arq Bras Endocrinol Metab

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A apoptose é um processo de morte celular que ocorre geralmente após a fragmentação progressiva do DNA e parece ser importante em tecidos normais e neoplásicos. Pouco é conhecido sobre a ocorrência da apoptose nas doenças da tiróide. A finalidade deste estudo é investigar um possível papel da apoptose no crescimento do carcinoma bem diferenciado de tiróide, usando um ensaio com nucleotidil transferase in situ (ENTIS), o qual detecta a fragmentação do DNA, para determinar a freqüência da apoptose no bócio colóide (BC), adenoma folicular (AF), carcinoma folicular (CF) e carcinoma papilar (CP). Os tecidos de BC (n=3), AF (n=2), CF (n=4) e CP (n=3) foram obtidos de ressecção cirúrgica em 12 pacientes. As células apoptóticas positivas (CAP) dentro do folícu-lo tiroidiano e tecido neoplásico foram contadas em áreas de 1 cm 2 . O teste T foi utilizado para testar a significância estatística. O número de CAPs foi significantemente maior (p<0,0001) nos BC e AF (24,4±8,2 CAP/cm 2 ) comparado com CF e CP (1,33±0,82 CAP/cm 2 ). Nenhuma diferença significativa foi vista no número de CAPs entre BC e AF e entre CF e CP. A apoptose pode desempenhar um importante papel na progressão do carcinoma bem diferenciado de tiróide, visto que no presente estudo o índice apoptótico foi muito baixo nessas neoplasias. A apoptose, diferentemente da necrose, é um processo ativo que poderia ser inibido ou induzido o que, neste caso, seria interessante para a terapêutica. (Arq Bras Endocrinol Metab 2000;44/2: 153-6)

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Apoptosis in Thyroid Tissue from Patients with Hashimoto's Thyroiditis

Cited by 100 publications

References 10 publications

Effect of ceramide on apoptosis and phospholipase D activity in FRTL-5 thyroid cells

Effect of ceramide on apoptosis and phospholipase D activity in FRTL-5 thyroid cells

Fas and Fas ligand gene expression in autoimmune thyroiditis in BB/W rats

Apoptose em tiroidopatias hiperplásias e neoplásicas

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