The clock gene Per2 is required for normal platelet formation and function

Zhao, Yue; Zhang, Ying; Wang, Shiming; Hua, Zichun; Zhang, Jianfa

doi:10.1016/j.thromres.2010.11.025

Cited by 22 publications

(18 citation statements)

References 50 publications

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“…After comprehensively surveying the links between PER2 and TP53 in previous reports [2,4,[9][10][11][12][13][14][15], we selected wild-type TP53 human U343 glioma cells, then RNA interference technology and shRNA-lentivirus were used to downregulate PER2. However, we found that following treatment with 6 mV, 100cGy of X-ray irradiation, DNA damage was observed in both two groups after 24 h, and shRNA-PER2-transfected cells showed more serious DNA tailing phenomena and significantly increased death rate compared with control cells.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, clear differences in PER2 expression are evident in tumor tissue and non-involved peripheral tissues [3][4][5][6][7]. Elsewhere, overexpression and/or or mutations in the PER2 gene have been reported to correlate with enhanced tumor growth in breast cancer, colon cancer and lymphoma, corresponding with altered expression of TP53 and the oncogenes BCLxl, BCL-2, cyclinB1, cyclin D, cyclin E and C-MYC [8][9][10][11][12][13][14][15]. PER2 has also been linked with DNA damage response pathways [16].…”

Section: Introductionmentioning

confidence: 99%

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Down-Regulation of PER2 Increases Apoptosis of Gliomas after X-Ray Irradiation

Li¹,

Liu²,

Xia³

et al. 2017

Chemotherapy (Los Angel)

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Period2 (PER2), a core circadian gene, not only modulates circadian rhythm but also may play an important role in other biological processes including pathways involved in the proliferation and apoptosis of tumor cells. In this study, we investigated the mechanism by which downregulated expression of PER2 promotes apoptosis of wild-type TP53 human glioma U343 cells exposed to X-rays. U343 cells were irradiated with 6mV 10Gy X-ray irradiation after infection with shRNA lentivirus to reduce expression of PER2, and then analyzed by several methods such as SCGE analysis, flow cytometry, RT-PCR, and western blotting. Compared with controls, U343 cells expressing low levels of PER2 showed serious DNA damage when exposed to X-ray irradiation in SCGE analysis (P<0.05), and higher death rates in flow cytometry assay (P<0.05). RT-PCR and western blot analysis both revealed decreased expression of ATM and TP53, which regulate DNA damage and repair via the ATM-TP53 pathway, and an increased expression of C-MYC, which is related to cell apoptosis. Thus, our research suggests that PER2 may play an important role in tumor radiotherapy, which is attributable to enhanced ATM-TP53 signaling and pro-apoptotic processes. These findings provide a new target for the clinical treatment of glioma, and a reliable basis for postradiation therapy and gene therapy for glioma and other cancers.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Down-Regulation of PER2 Increases Apoptosis of Gliomas after X-Ray Irradiation

Li¹,

Liu²,

Xia³

et al. 2017

Chemotherapy (Los Angel)

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“…The clock gene per2 modulating the apoptosis of megakaryocytes yet again specified the multifunctional role of biological clock in immune functions. The platelet formation from megakaryocytes, DNA synthesis in megakaryotes, quantity of reticulate platelets, levels of plasma thrombopoietin and mean size of mature megakaryocytes are circadian (Zhao et al 2011) and implying potential control of circadian clock in platelet formation and function (Zhao et al 2011). Deficiency of the clock gene Bmal1 in knockout mice resulted in chronic inflammation, decreased lymphocyte and increased neutrophil counts (Kondratov et al 2006); Cry1 and Cry2 knockout mice showed increased TNFα synthesis (Hashiramoto et al 2010).…”

Section: Circadian Immune Functions and Carcinogenesismentioning

confidence: 99%

Chronotherapy: a noteworthy focal point in the treatment of cancer?

Subramanian

Jayapalan

Hashim

2014

Biological Rhythm Research

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In mammalian systems including humans, DNA synthesis, cell cycle and mitotic index are circadian in nature. Disrupted circadian clock leads to disturbed cellular rhythms, metabolism and hormonal balance and is noticeably accountable for the uncontrolled cell division ultimately leading to cancer. About a decade ago, there are fewer evidences on the role of biological clock on tumorigenesis. Currently, a relationship between shift work and cancer, distinctively breast cancer in women and prostate cancer in men, distraction of sleep-wake cycles and augmentation of cancer development, oncostatic effects of melatonin (the internal zeitgeber of circadian system), bidirectional relationships of circadian and immune systems, the prospect of clock genes as tumour suppressors, inaccurate temporal management of oxidative stress and genotoxicity have been recounted, making the crucial role of circadian clock in carcinogenesis. This review critically evaluates present knowledge on circadian rhythms in relation to cancer and its management. The accumulating and coercing evidences could be valuable in formulating the rhythm-based therapy as a remarkable focal point in the management of cancer.

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“…Several factors that affect megakaryocyte development are known to exhibit diurnal rhythmicity. First, the cytokine principally responsible for megakaryocyte recruitment and development, thrombopoietin (Thpo), exhibits a diurnal pattern of gene expression in murine liver [2,3], that is associated with diurnal fluctuations in plasma protein levels [4,5]. Second, the expression of stromal derived factor 1 (Cxcl12; a chemokine required for megakaryocyte relocation to The mammalian circadian clock is a transcription-translation feedback loop that drives the rhythmic expression of many genes in many different cell types.…”

Section: Megakaryopoiesis Is Rhythmicmentioning

confidence: 99%

“…Mice expressing a dominant negative form of CLOCK (CLOCK D19/D19 ) exhibit reduced platelet counts [11], whereas in Per2-null mice, circulating platelet numbers are reduced by 50% [5]. Interestingly, the temporal pattern of Thpo expression in the livers of Per2-null mice is disrupted and marrow cMpl expression is significantly increased.…”

Section: Experimental Modulation Of Core Clock Genes and The Plateletmentioning

confidence: 99%

The diurnal tick-tockery of platelet biology

Hartley

2011

Platelets

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Circadian (∼24 hours) clocks are ubiquitous in nature and are important regulators of behaviour, physiology and metabolism. Circadian clocks can synchronise biological processes with environmental cycles, buffer biological systems to maintain homeostasis and partition mutually antagonistic processes to different temporal spaces within the daily cycle. Clocks act cell-autonomously (intrinsically) and systemically (extrinsically) to coordinate whole organism biology and there is epidemiological evidence indicating that chronic disruption of behavioural rhythms increases the risk of developing cancer and cardiovascular disease. Although the genetic mechanism of the mammalian clock has been largely deciphered, the physiological relevance of clocks often remains elusive. Findings from humans and animal models suggest that the circadian clock and diurnal rhythms have an important role in megakaryopoiesis and the risk of a cardiovascular event. This short review will introduce the mammalian circadian clock and discuss how circadian clocks and diurnal rhythms influence platelet production and function.

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The clock gene Per2 is required for normal platelet formation and function

Cited by 22 publications

References 50 publications

Down-Regulation of PER2 Increases Apoptosis of Gliomas after X-Ray Irradiation

Down-Regulation of PER2 Increases Apoptosis of Gliomas after X-Ray Irradiation

Chronotherapy: a noteworthy focal point in the treatment of cancer?

The diurnal tick-tockery of platelet biology

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