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学科主题: 临床医学
题名:
PDIp is a major intracellular oestrogen-storage protein that modulates tissue levels of oestrogen in the pancreas
作者: Fu, Xinmiao1,2; Wang, Pan1; Fukui, Masayuki1; Long, Cheng3; Yin, Linxiang4; Choi, Hye Joung1; Zhu, Bao Ting1
关键词: 17 beta-oestradiol (E-2) ; oestrogen ; oestrogen receptor ; pancreas ; pancreas-specific protein disulfide isomerase (PDIp)
刊名: BIOCHEMICAL JOURNAL
发表日期: 2012-10-01
DOI: 10.1042/BJ20120868
卷: 447, 页:115-123
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology
研究领域[WOS]: Biochemistry & Molecular Biology
关键词[WOS]: ESTRADIOL-BINDING PROTEIN ; DISULFIDE-ISOMERASE ; RECEPTOR-ALPHA ; INSULIN-SECRETION ; EXOCRINE PANCREAS ; TARGET-CELLS ; ACINAR-CELLS ; BETA-CELLS ; CANCER ; LOCALIZATION
英文摘要:

E-2 (17 beta-oestradiol), a female sex hormone, has important biological functions in a woman′s body. The pancreas, often considered a non-classical E-2-targeting organ, is known to be functionally regulated by E-2, but little is known about how oestrogen actions are regulated in this organ. In the present study we report that PDIp (pancreas-specific protein disulfide isomerase), a protein-folding catalyst, can act as a major intracellular E-2 storage protein in a rat model to modulate the pancreatic tissue level, metabolism and action of E-2. The purified endogenous PDIp from both rat and human pancreatic tissues can bind E-2 with a K-d value of approximately 150 nM. The endogenous PDIp-bound E-2 accounts for over 80% of the total protein-bound E-2 present in rat and human pancreatic tissues, and this binding protects E-2 from metabolic disposition and prolongs its duration of action. Importantly, we showed in ovariectomized female rats that the E2 level in the pancreas reaches its highest level (9-fold increase over its basal level) at 24-48 h after a single injection of E-2, and even at 96 h its level is still approximately 5-fold higher. In contrast, the E-2 level in the uterus quickly returns to its basal level at 48 h after reaching its maximal level (approximately 2-fold increase) at 24 h. Taken together, these results show for the first time that PDIp is a predominant intracellular oestrogen storage protein in the pancreas, which offers novel mechanistic insights into the accumulation and action of oestrogen inside pancreatic cells.

语种: 英语
所属项目编号: R01CA97109 ; 31100559 ; P20RR021940
项目资助者: National Institutes of Health ; National Natural Science Foundation of China ; National Center for Research Resources
WOS记录号: WOS:000309489600012
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/54176
Appears in Collections:北京大学第三临床医学院_期刊论文

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作者单位: 1.Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Sch Med, Kansas City, KS 66160 USA
2.Peking Univ, Sch Life Sci, State Key Lab Prot & Plant Gene Res, Beijing 100871, Peoples R China
3.Peking Univ, Hosp 3, Spine Tumor Ctr, Beijing 100871, Peoples R China
4.China Agr Univ, Coll Biol Sci, Beijing 100094, Peoples R China

Recommended Citation:
Fu, Xinmiao,Wang, Pan,Fukui, Masayuki,et al. PDIp is a major intracellular oestrogen-storage protein that modulates tissue levels of oestrogen in the pancreas[J]. BIOCHEMICAL JOURNAL,2012,447:115-123.
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