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EXPRESSION PROFILING REVEALS A POSITIVE REGULATION BY MPER2 ON CIRCADIAN RHYTHM OF CYTOTOXICITY RECEPTORS: LY49C AND NKG2D
Luo, Yonglun1,3; Tian, Weiping1; Cai, Lun2; Wang, Yan1; Zhang, Jing1; Teng, Huajing1; Du, Jie1,2; Sun, Zhong Sheng1,3; Zhong ShengSun
2009
Source PublicationCHRONOBIOLOGY INTERNATIONAL
ISSN0742-0528
SubtypeArticle
Volume26Issue:8Pages:1514-1544
AbstractThe mammalian circadian gene, mPer2, an indispensable component of the mammalian circadian clock, not only modulates endogenous circadian rhythms but also plays a crucial role in regulating innate immune function. Previously, we showed that mPer2 plays a crucial role in regulating cytotoxic response. To investigate the molecular mechanism for mPer2-controlled cytotoxic response, in the present study we conducted mRNA expression for 11 genes participating in cytotoxicity regulation in wild-type (WT) and mPer2 knockout (mPer2  −; ; /  −; ; ) mice bone marrow, that is, Dap-10, Ly49C, Ly49I, Rac1, Mapk1, Map2k1, Nkg2d, Shp-1, Pak1, Pik3ca, and Vav1. The mRNA levels of Ly49C (p < 0.001), Ly49I (p = 0.039), and Nkg2d (p = 0.038) were significantly downregulated in mPer2  −; ; /  −; ;  mice. Time-dependence of expression profiling was then conducted for four core clock genes (Per1, Bmal1, Clock, Rev-erbα), and six out of these 11 cytotoxic regulation genes (Ly49C, Ly49I, Mapk1, Nkg2d, Shp-1, Pik3ca) in WT and mPer2  −; ; /  −; ;  entrained in light/dark (LD) or dark/dark (DD) cycles. Consistently, circadian oscillations were observed for Per1, Rev-erbα, Ly49C, and Nkg2d in WT mice under LD and DD cycles. However, these rhythmic expressions were either disrupted or dampened in mPer2  −; ; /  −; ;  mice. Comparison of gene expression between WT and mPer2  −; ; /  −; ;  mice showed that mPer2 knockout had systematically downregulated the mRNA expression of two cytotoxicity regulators, Ly49C and Nkg2d. FACS analysis further confirmed that the circadian expression of these genes was not due to the daily difference in cell numbers of NK, NKT, or T cells in bone marrow. Taken together, our results reveal that mPer2 is a critical clock component in modulating circadian rhythms in bone marrow. Furthermore, it implies that Ly49C and Nkg2d are two clock-controlled genes that may play an important role in mediating mPer2-controlled cytotoxic response.; The mammalian circadian gene, mPer2, an indispensable component of the mammalian circadian clock, not only modulates endogenous circadian rhythms but also plays a crucial role in regulating innate immune function. Previously, we showed that mPer2 plays a crucial role in regulating cytotoxic response. To investigate the molecular mechanism for mPer2-controlled cytotoxic response, in the present study we conducted mRNA expression for 11 genes participating in cytotoxicity regulation in wild-type (WT) and mPer2 knockout (mPer2(-/-)) mice bone marrow, that is, Dap-10, Ly49C, Ly49I Rac1, Mapk1, Map2k1, Nkg2d, Shp-1, Pak1, Pik3ca, and Vav1. The mRNA levels of Ly49C (p < 0.001), Ly49I (p = 0.039), and Nkg2d (p = 0.038) were significantly downregulated in mPer2(-/-) mice. Time-dependence of expression profiling was then conducted for four core clock genes (Per1, Bmal1, Clock, Rev-erb alpha), and six out of these 11 cytotoxic regulation genes (Ly49C, Ly49I, Mapk1, Nkg2d, Shp-1, Pik3ca) in WT and mPer2(-/-) entrained in light/dark (LD) or dark/dark (DD) cycles. Consistently, circadian oscillations were observed for Per1, Rev-erb alpha, Ly49C, and Nkg2d in WT mice under LD and DD cycles. However, these rhythmic expressions were either disrupted or dampened in mPer2(-/-) mice. Comparison of gene expression between WT and mPer2(-/-) mice showed that mPer2 knockout had systematically downregulated the mRNA expression of two cytotoxicity regulators, Ly49C and Nkg2d. FACS analysis further confirmed that the circadian expression of these genes was not due to the daily difference in cell numbers of NK, NKT, or T cells in bone marrow. Taken together, our results reveal that mPer2 is a critical clock component in modulating circadian rhythms in bone marrow. Furthermore, it implies that Ly49C and Nkg2d are two clock-controlled genes that may play an important role in mediating mPer2-controlled cytotoxic response. (Author correspondence: zsunusa@yahoo.com)
KeywordCytotoxicity regulation Cytotoxicity receptors mPer2 Ly49C Nkg2d
Subject Area遗传学
Indexed BySCI
Language英语
WOS IDWOS:000279983800002
Citation statistics
Cited Times:11[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.psych.ac.cn/handle/311026/5405
Collection中国科学院心理研究所回溯数据库(1956-2010)
Corresponding AuthorZhong ShengSun
Affiliation1.Chinese Acad Sci, Behav Genet Ctr, Inst Psychol, Beijing 101300, Peoples R China
2.Capital Med Univ, Beijing Anzhen Hosp, Beijing Inst Heart Lung & Blood Vessel Dis, Beijing, Peoples R China
3.Chinese Acad Sci, Grad Univ, Beijing 101300, Peoples R China
Recommended Citation
GB/T 7714
Luo, Yonglun,Tian, Weiping,Cai, Lun,et al. EXPRESSION PROFILING REVEALS A POSITIVE REGULATION BY MPER2 ON CIRCADIAN RHYTHM OF CYTOTOXICITY RECEPTORS: LY49C AND NKG2D[J]. CHRONOBIOLOGY INTERNATIONAL,2009,26(8):1514-1544.
APA Luo, Yonglun.,Tian, Weiping.,Cai, Lun.,Wang, Yan.,Zhang, Jing.,...&Zhong ShengSun.(2009).EXPRESSION PROFILING REVEALS A POSITIVE REGULATION BY MPER2 ON CIRCADIAN RHYTHM OF CYTOTOXICITY RECEPTORS: LY49C AND NKG2D.CHRONOBIOLOGY INTERNATIONAL,26(8),1514-1544.
MLA Luo, Yonglun,et al."EXPRESSION PROFILING REVEALS A POSITIVE REGULATION BY MPER2 ON CIRCADIAN RHYTHM OF CYTOTOXICITY RECEPTORS: LY49C AND NKG2D".CHRONOBIOLOGY INTERNATIONAL 26.8(2009):1514-1544.
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