Inhibitory Effect of Thyrotropic Hormone on Apoptosis Induced by Actinomycin D in a Functioning Rat Thyroid Cell Line.

Sato, Haru–Tada; Abe, Yoshifumi; Noguchi, M.; Kurokawa, Kiyoshi; Sakai, Hideto

doi:10.1507/endocrj.46.309

Cited by 7 publications

(3 citation statements)

References 17 publications

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“…Apoptosis results also from the loss of normal integrin-fibronectin interactions (anoikis) , and is prevented by TSH (Li et al 1999, Sato et al 1999. In addition, when thyroid follicles are cultured in a three-dimensional system, even withdrawal of TSH or other growth factors does not induce apoptosis (Bechtner et al 1999) suggesting that two-dimensional models of cultured thyrocytes do not reflect the in vivo regulation of apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Cell necrosis and apoptosis are differentially regulated during goitre development and iodine-induced involution

Mutaku

Poma²,

Many

et al. 2002

Journal of Endocrinology

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Necrosis and apoptosis coexist in the thyroid during goitre development and involution, but little is known about their respective causes. To test the possible role of free radicals, we analysed separately necrosis and apoptosis in male Wistar rats with depressed or normal antioxidant protection. Vitamin E-deficient and -sufficient rats were made goitrous with perchlorate in drinking water; involution was induced by repeated injection of NaI, without or with methimazole. Increase of thyroid malondialdehyde concentration and decrease of glutathione peroxidase activity confirmed the depressed antioxidant protection in vitamin E-deficient rats. Plasma thyroxine and TSH levels were not modified. Necrosis (swollen cells) and apoptosis (pyknotic cells) were quantified on histological sections. In vitamin E-sufficient rats, dead cells were very rare in control thyroids, increased 3-fold in goitre and still further during involution.Necrotic epithelial cells predominated in the goitre and their number declined after iodide supplementation, without or with methimazole. In contrast, the number of apoptotic cells and the caspase-3 activity were increased in goitre and further increased after involution, with twothirds of pyknotic cells being observed in the interstitium. Apoptosis was prevented by methimazole. Vitamin E deficiency significantly increased total cell death and epithelial cell necrosis and induced the occurrence of much cell debris in the follicular lumen during involution, with no modification of the apoptotic reaction. These results show that the type of cell death is differentially regulated during goitre development and involution: necrosis is related to the oxidative status of the cells, while apoptosis comes with iodine-induced involution.

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Section: Introductionmentioning

confidence: 99%

Cell necrosis and apoptosis are differentially regulated during goitre development and iodine-induced involution

Mutaku

Poma²,

Many

et al. 2002

Journal of Endocrinology

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“…The thyroid cells are very sensitive to UV radiations or other substances known as oxidative stress inducers such as BSO or hydrogen peroxide [15,16,19] . Little is known, however, about the UV irradiation response and its regulation in normal human thyroid cells [17] , because the majority of studies reported in the literature feature tumor cells or other human cell types [7,20] . Therefore, the aim of this study was to examine how UVC irradiation aff ects normal human thyroid cell proliferation and HLA-DR expression.…”

Section: Discussion ▼mentioning

confidence: 99%

UVC Radiation-induced Effect on Human Primary Thyroid Cell Proliferation and HLA-DR Expression

Kostić¹,

Toffoletto²,

Toller³

et al. 2010

Horm Metab Res

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The aim of this study was to examine how UVC irradiation will affect normal human thyroid cell proliferation and HLA-DR expression. Primary human thyroid cells were exposed to UVC (254 nm wavelength) irradiation. In some experiments 0.5 mM buthionine sulfoximine (BSO) was added. Apoptosis was detected measuring annexin V, proteins involved in apoptotic process (p53, Bax, Bcl-2, caspase 3, and 9) by immunoblot analysis and HLA-DR expression by FACS. UVC induced a cell cycle arrest in G0/G1 phase in the first 24 h, accumulation of cells in the S phase 72 h after treatment, and an increase of apoptotic cells. BSO pretreatment showed an earlier appearance and a higher percentage of apoptosis. p53, caspase 3 and 9 were increased, while Bax and Bcl-2 were decreased. We also observed a transient significant increase in HLA-DR expression. UVC inhibited cell proliferation and induced apoptosis in normal human primary thyroid cells. An inhibitor of glutathione synthesis induced an earlier appearance and higher percentage of apoptosis suggesting that oxidative stress may play a role. Apoptotis involved components of the intrinsic mitochondrial pathway. A transient increase in HLA-DR expression after UVC irradiation could play a role in inducing AITD.

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“…Moreover, it stabilizes cleavable topoisomerase I and II complexes with DNA, in which the polypeptide lactone rings occupy a position in the minor groove of the DNA helix or the drug penetrates the topoisomerase-DNA binding area [ 11 , 12 ]. After years of Actinomycin D usage, its action was also correlated with apoptosis; at low doses, the drug is a potent inducer of apoptosis [ 13 , 14 ], triggering this process in normal and tumor cells, as well as in cells that rarely undergo apoptosis [ 15 ]. It was shown that the molecular mechanism of Actinomycin D-induced apoptosis was associated with activation of the apoptosis FAS surface protein, which is also known as CD95 (cluster of differentiation 95) [ 16 ], the non-mitochondrial stress-activated protein/Junmino-terminal kinases apoptotic pathway, and with increased expression of the apoptosis regulator BAX [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Neutral metalloaminopeptidases APN and MetAP2 as newly discovered anticancer molecular targets of actinomycin D and its simple analogs

et al. 2018

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The potent transcription inhibitor Actinomycin D is used with several cancers. Here, we report the discovery that this naturally occurring antibiotic inhibits two human neutral aminopeptidases, the cell-surface alanine aminopeptidase and intracellular methionine aminopeptidase type 2. These metallo-containing exopeptidases participate in tumor cell expansion and motility and are targets for anticancer therapies. We show that the peptide portions of Actinomycin D and Actinomycin X2 are not required for effective inhibition, but the loss of these regions changes the mechanism of interaction. Two structurally less complex Actinomycin D analogs containing the phenoxazone chromophores, Questiomycin A and Actinocin, appear to be competitive inhibitors of both aminopeptidases, with potencies similar to the non-competitive macrocyclic parent compound (Ki in the micromolar range). The mode of action for all four compounds and both enzymes was demonstrated by molecular modeling and docking in the corresponding active sites. This knowledge gives new perspectives to Actinomycin D's action on tumors and suggests new avenues and molecules for medical applications.

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Inhibitory Effect of Thyrotropic Hormone on Apoptosis Induced by Actinomycin D in a Functioning Rat Thyroid Cell Line.

Cited by 7 publications

References 17 publications

Cell necrosis and apoptosis are differentially regulated during goitre development and iodine-induced involution

Cell necrosis and apoptosis are differentially regulated during goitre development and iodine-induced involution

UVC Radiation-induced Effect on Human Primary Thyroid Cell Proliferation and HLA-DR Expression

Neutral metalloaminopeptidases APN and MetAP2 as newly discovered anticancer molecular targets of actinomycin D and its simple analogs

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