The C-<i>Erb</i>Aβ Thyroid Hormone Receptor Expression and cDNA sequence analysis of the hormone-binding domain in human cancer cell lines

Chow, Vincent T.K.; Lim, SeonHee; Tock, E. P. C.

doi:10.3109/02841869409083925

Cited by 3 publications

(2 citation statements)

References 26 publications

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“…The presence of the red dots indicates that LC3 is present within lysosomes, since autophagosomes are able to fuse with lysosomes due to autophagic flux. We also tested the ability of T 3 to promote autophagy in several other hepatic cell lines, AML-12, Hep3B, and Huh7, that contain endogenous TRs at detectable protein levels (23,28,29). We observed that T 3 significantly increased LC3-II levels in these cells, further confirming that T 3 is proautophagic in hepatic cells (Figure 2, D and E).…”

Section: Introductionsupporting

confidence: 55%

Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy

et al. 2012

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For more than a century, thyroid hormones (THs) have been known to exert powerful catabolic effects, leading to weight loss. Although much has been learned about the molecular mechanisms used by TH receptors (TRs) to regulate gene expression, little is known about the mechanisms by which THs increase oxidative metabolism. Here, we report that TH stimulation of fatty acid β-oxidation is coupled with induction of hepatic autophagy to deliver fatty acids to mitochondria in cell culture and in vivo. Furthermore, blockade of autophagy by autophagy-related 5 (ATG5) siRNA markedly decreased TH-mediated fatty acid β-oxidation in cell culture and in vivo. Consistent with this model, autophagy was altered in livers of mice expressing a mutant TR that causes resistance to the actions of TH as well as in mice with mutant nuclear receptor corepressor (NCoR). These results demonstrate that THs can regulate lipid homeostasis via autophagy and help to explain how THs increase oxidative metabolism. IntroductionThyroid hormones (THs) have been known to stimulate basal metabolic rate for over a century (1, 2). Subsequent studies showed that THs induced energy expenditure in response to increased caloric intake (3). Later, several intracellular processes were shown to be involved in the calorigenic effects of THs. These included increased ATP expenditure due to increased Na + /K + -ATPase activity to maintain ion gradients in various tissues (4, 5) as well as reduced efficiency of ATP synthesis, particularly through the induction of uncoupling proteins (UCPs), which cause proton leakage in the electron transport chain of the mitochondria of target tissues (6, 7). However, despite these advances in our understanding of THs on cellular metabolism, none of these proposed mechanisms appears to be dominant. Currently, little is known about other mechanisms that might be utilized by THs to regulate energy consumption within the cell. This is particularly true for the events involved in the delivery of fatty acids to mitochondria, a necessary step in converting stored intracellular triglyceride fuel into ATP.The active form of TH, 3,3′5-triiodo-l-thyronine (T 3 ), is a critical regulator of cellular and tissue metabolism throughout the body. It controls gene expression in target tissues by binding to its cognate nuclear receptors (TRα and TRβ), which are ligand-inducible transcription factors. In the presence of T 3 , TH receptors (TRs) bind to TH response elements in the promoters of target genes and form coactivator complexes containing histone acetyltransferase activity to activate transcription (8). In the absence of T 3 , TRs recruit corepressors such as NCoR and silencing mediator of retinoid and thyroid receptors (SMRT), which together with transducin β-like protein 1 (TBL1) and histone deacetylase 3 (HDAC3)

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Section: Introductionsupporting

confidence: 55%

Thyroid hormone stimulates hepatic lipid catabolism via activation of autophagy

et al. 2012

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“…These ligand-dependent transcription factors bind to specific hormone responsive element DNA sequences, thereby modulating complex programs of expression of specific target genes to regulate many aspects of vertebrate development, differentiation, and homeostasis. A previous study employed a pair of primers, ERA1 and ERA2, designed to amplify a 438-bp fragment within the hormone-binding domain of the c-erbA␤ gene of human cell lines (Chow et al, 1994). RT-PCR of MRC-5 human embryonic lung cells using this primer pair generated an equally prominent ϳ350-bp product, in addition to the target 438-bp fragment.…”

Section: Introductionmentioning

confidence: 99%