DEC2 modulates orexin expression and regulates sleep

Hirano, Arisa; Hsu, Pei Ken; Zhang, Luoying; Xing, Lijuan; McMahon, Thomas; Yamazaki, Maya; Ptáček, Louis J.; Fu, Ying Hui

doi:10.1073/pnas.1801693115

Cited by 61 publications

(59 citation statements)

References 38 publications

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“…This suggests that the mutant sleep phenotype involves clock gene function outside of their central time-keeping role. Interestingly mutations in some of the circadian transcription factors we identified, Per3 and Dec2, indeed lead to deficits in sleep regulation (Archer et al, 2018;He et al, 2009;Hirano et al, 2018). Our results support a role of clock genes in influencing sleep outside of their roles in generating circadian rhythms (Franken, 2013).…”

Section: Wild Type Shank3supporting

confidence: 69%

Shank3 Modulates Sleep and Expression of Circadian Transcription Factors

Ingiosi

Wintler

Schoch

et al. 2018

Preprint

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Autism Spectrum Disorder (ASD) is the most prevalent neurodevelopmental disorder in the United States and often co-presents with sleep problems. Sleep problems in ASD predict the severity of ASD core diagnostic symptoms and have a considerable impact on the quality of life of caregivers. Little is known, however, about the underlying molecular mechanisms. We investigated the role of Shank3, a high confidence ASD gene candidate, in sleep architecture and regulation. We show that mice lacking exon 21 of Shank3 have problems falling asleep even when sleepy. Using RNA-seq we show that sleep deprivation increases the differences in gene expression between mutants and wild types, downregulating circadian transcription factors Per3, Dec2, Hlf, Tef, and Reverbα. Shank3 mutants also have trouble regulating wheel-running activity in constant darkness. Overall our study shows that Shank3 is an important modulator of sleep and clock gene expression.

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Section: Wild Type Shank3supporting

confidence: 69%

Shank3 Modulates Sleep and Expression of Circadian Transcription Factors

Ingiosi

Wintler

Schoch

et al. 2018

Preprint

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“…More recent studies on the physiology of orexins have indeed shown a tight interaction between sleep‐wake state and feeding behaviour. Studies by Hirano et al reported that Basic helix‐loop‐helix family, member e41 (BHLHE41, DEC2) regulates sleep‐wake state via orexin. DEC2 is highly expressed by neurons of the suprachiasmatic nucleus of the hypothalamus, the brain region responsible for circadian clock.…”

Section: Interaction Between Eating Behaviour and Sleepmentioning

confidence: 99%

Hypocretin/orexin modulates body weight and the metabolism of glucose and insulin

Adeghate

Lotfy

D’Souza

et al. 2020

Diabetes Metabolism Res

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Summary The hypocretin/orexin (Hcrt/orexin) unit affects the functions of the nervous, cardiovascular, gastrointestinal, and reproductive systems. Hcrt/orexin ligands and receptors have been localized to different parts of the central and peripheral nervous systems, cerebrospinal fluid and blood, exocrine (pancreas, salivary, lacrimal) as well as endocrine (pancreatic islets, pituitary, adrenal) glands. Several factors including stress, glucagon‐like peptide‐1 agonists, glutamate, nicotine, glucose, and hypoglycaemia stimulate the expression of Hcrt/orexin system, but it is inhibited by ageing, bone morphogenetic protein, hypoxia/hypercapnia, melanocortin receptor accessory protein 2, and glucagon. Literature reports show that Hcrt/orexin can significantly increase insulin secretion from normal and diabetic rat pancreata. Hcrt/orexin decreases blood glucose concentration and reduces insulin resistance partly via increased tissue expression of glucose transporter type 4. It reduces obesity by increasing browning of fat cells and energy expenditure. Taken together, Hcrt/orexin modulates obesity and the metabolism of glucose and insulin. The Hcrt/orexin system may thus be a target in the development of new therapies for the treatment of diabetes mellitus.

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“…The total protein extraction was performed using a lysis buffer (Pierce). The total protein concentration in the extract was estimated by the Bradford method . A total of 15 μg of protein per sample were separated via 15%, 10% or 8% SDS‐PAGE, and transferred onto polyvinylidene fluoride membranes (PVDF; Millipore).…”

Section: Methodsmentioning

confidence: 99%

“…For the former, BHLHE41 protein re‐enters the nucleus after transcription and translation and competes with CLOCK‐BMAL1 heterodimer for E‐Box element binding (through competitive inhibition). BHLHE41 functions as a suppressor of circadian rhythm regulation in this process . For non‐circadian regulation, BHLHE41 is implicated in multiple other pathways, such as BCR, notch, hypoxia, ERK/NF‐kappaB and PI3K/Akt pathways …”

Section: Introductionmentioning

confidence: 99%

BHLHE41 suppresses MCF‐7 cell invasion via MAPK/JNK pathway

Zhang

Zheng

Wang

et al. 2020

J Cellular Molecular Medi

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| 4001 wileyonlinelibrary.com/journal/jcmm | INTRODUC TI ONBasic helix-loop-helix family member e41 (BHLHE41, also known as SHARP1, DEC2 and BHLHB3) is mapped to human chromosome 12p12.1. It serves an important role in regulating cell differentiation, maintaining circadian rhythm, apoptosis, hypoxia and immune response. [1][2][3][4][5][6][7][8][9][10][11] The major functions of BHLHE41 are divided into two categories: circadian and non-circadian regulation. For the former, BHLHE41 protein re-enters the nucleus after transcription and translation and competes with CLOCK-BMAL1 heterodimer for E-Box element binding (through competitive inhibition). BHLHE41 functions as a suppressor of circadian rhythm regulation in this process. 11,12 For non-circadian regulation, BHLHE41 is implicated in multiple other pathways, such as BCR, notch, hypoxia, ERK/NF-kappaB and PI3K/Akt pathways. 3,6,8,[13][14][15] Dysregulation of BHLHE41 transcription levels has been characterized as a marker of the progression of several cancers. 8,[16][17][18][19][20][21][22][23] Abstract Deregulation of the basic helix-loop-helix family member e41 (BHLHE41) has been characterized as a marker of progression of several cancers. In this study, we aimed to explore the mechanism by which BHLHE41 regulates the invasion of breast cancer cells. BHLHE41 suppresses, whereas the silencing of BHLHE41 promotes tumour invasion of both MCF-7 and MDA-MB-231 cells. Meanwhile, BHLHE41 down-regulated the transcription and translation of SNAI1, SNAI2, VIM and CDH2, and up-regulated those of CLDN1, CLDN4 and CDH1. Reporter assay indicated that silencing of BHLHE41 dramatically activated the MAPK/JNK signalling pathway in MCF-7 cell line and the hypoxia signalling pathway in MDA-MB-231 cell line. Furthermore, silencing of BHLHE41 activated the MAPK/JNK signalling pathway by up-regulating phosphorylated JNK and failed to affect the expression of HIF-1 alpha in MCF-7 cells. After blocking the MAPK/JNK signalling pathway by specific inhibitor SP600125, silencing of BHLHE41 failed to promote tumour cell invasion. These results suggest that BHLHE41 facilitates MCF-7 cell invasion mainly via the activation of MAPK/ JNK signalling pathway. In conclusion, although BHLHE41 suppresses tumour invasion in MCF-7 and MDA-MB-231 cell lines, the specific regulatory mechanisms may be different. K E Y W O R D S BHLHE41, breast cancer, invasion, JNK signalling pathway, tight junction How to cite this article: Zhang D, Zheng Q, Wang C, Zhao N, Liu Y, Wang E. BHLHE41 suppresses MCF-7 cell invasion via MAPK/JNK pathway.

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DEC2 modulates orexin expression and regulates sleep

Cited by 61 publications

References 38 publications

Shank3 Modulates Sleep and Expression of Circadian Transcription Factors

Shank3 Modulates Sleep and Expression of Circadian Transcription Factors

Hypocretin/orexin modulates body weight and the metabolism of glucose and insulin

BHLHE41 suppresses MCF‐7 cell invasion via MAPK/JNK pathway

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