WordNet

exert oneself to meet a challenge; "rise to a challenge"; "rise to the occasion"
increase in value or to a higher point; "prices climbed steeply"; "the value of our house rose sharply last year" (同)go_up, climb
rise in rank or status; "Her new novel jumped high on the bestseller list" (同)jump, climb up
the act of changing location in an upward direction (同)ascent, ascension, ascending
an increase in cost; "they asked for a 10% rise in rates" (同)boost, hike, cost increase
a movement upward; "they cheered the rise of the hot-air balloon" (同)rising, ascent, ascension
a growth in strength or number or importance
come up, of celestial bodies; "The sun also rises"; "The sun uprising sees the dusk night fled..."; "Jupiter ascends" (同)come_up, uprise, ascend
move upward; "The fog lifted"; "The smoke arose from the forest fire"; "The mist uprose from the meadows" (同)lift, arise, move up, go_up, come_up, uprise
rise up; "The building rose before them" (同)lift, rear
increase in volume; "the dough rose slowly in the warm room" (同)prove
become heartened or elated; "Her spirits rose when she heard the good news"
earn on some commercial or business transaction; earn as salary or wages; "How much do you make a month in your new job?"; "She earns a lot in her new job"; "this merger brought in lots of money"; "He clears $5,000 each month" (同)take_in, clear, make, earn, realize, realise, pull_in, bring_in
increase or develop; "the peace movement gained momentum"; "the car gathers speed" (同)gather
increase (ones body weight); "She gained 20 pounds when she stopped exercising" (同)put_on
the amount by which the revenue of a business exceeds its cost of operating
obtain advantages, such as points, etc.; "The home team was gaining ground"; "After defeating the Knicks, the Blazers pulled ahead of the Lakers in the battle for the number-one playoff berth in the Western Conference" (同)advance, win, pull ahead, make headway, get ahead, gain ground
a process of becoming larger or longer or more numerous or more important; "the increase in unemployment"; "the growth of population" (同)increment, growth
become bigger or greater in amount; "The amount of work increased"
make bigger or more; "The boss finally increased her salary"; "The university increased the number of students it admitted"
the amount by which something increases; "they proposed an increase of 15 percent in the fare" (同)increment
the act of increasing something; "he gave me an increase in salary" (同)step-up
a change resulting in an increase; "the increase is scheduled for next month"
in several ways; in a multiple manner; "they were multiply checked for errors"
combine or increase by multiplication; "He managed to multiply his profits" (同)manifold
combine by multiplication; "multiply 10 by 15"

PrepTutorEJDIC

《文》『立ち上がる』《+『up』》 / 《文》『起床する』,起きる / (下から上へ)『上がる』,上昇する,昇る / 〈土地が〉上り[坂]になる / 〈山・建物などが〉そびえ立つ(進行形にできない) / 〈…の数量・価値・程度・力などが〉増す,増大する,増加する / 〈地位・身分などが〉(…から…へ)上がる,高くなる《+『from』+『名』+『to』+『名』》 / 〈川などが〉高さを増す,増水する / 〈パンなどが〉ふくれる / (…に)源を発する,始まる《+『from』(『in』)+『名』》(進行形にできない) / (…に)反乱を起こす,背いて立ち上がる《+『against』+『名』》 / 生き返る,よみがえる / (表面に)浮かび上がる / (…に)応じて立ち上がる,うまく対処する《+『to』+『名』》 / 〈C〉(…の)『上昇』《+『of』+『名』》 / 〈C〉(数量・価値・程度などの)増大,増加《+『in』(『of』)+『名』》 / 〈U〉立身;繁栄 / 〈C〉(…の)上り坂,上り勾配(こうばい)《+『in』(『of』)+『名』》 / 〈C〉丘,高台 / 〈C〉(…の)起源,始まり《+『of』+『名』》 / 《英話》昇給,昇給額(《米》raise) / 〈C〉魚がえさを求めて水面に浮き上がること
(努力して)…‘を'『得る』,手に入れる / …‘を'『増す』 / 〈競争など〉‘に'勝つ;〈賞など〉‘を'勝ち取る / 《文》(特に努力をして)〈目指す場所〉‘に'到達する;〈目的など〉‘を'達成する / 得をする / (…において)進歩する,よくなる,向上する;(体重・身長・能力など)増す《+in+名》 / 〈時計が〉進む / 〈C〉(…に)加えたもの《+『to』+『名』》;(…において)増加したもの《+『in』+『名』》 / 《複数形で》『利益』(profits);賞金 / 〈U〉利益を得ること,獲得
『増える』,『増大する』 / (…に)…‘を'『増やす』《+『名』+『to』+『名』》 / (…の)『増加』,増大;〈C〉増加量(額)《+『of』(『in』,『on』)+『名』》
…‘を'『増す』,ふやす;…‘を'繁殖させる / (ある数を)〈ある数〉‘に'『掛ける』《+『名』〈被乗数〉+『by』+『名』〈乗数〉》 / 〈数・量などが〉『ふえる』,増大する;繁殖する / 掛け算をする
多様に,複雑に,複合的に
(ある高さに)…‘を'『上げる』,‘の'程度を高める《『名』+『to』+『名』》 / (知的・精神的に)…‘を'向上させる,高める / (…から…に)〈人〉‘を'昇進させる《+『from』+『名』+『to』+『名』》

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/11/19 14:47:19」(JST)

wiki en

[Wiki en表示]

Downregulation is the process by which a cell decreases the quantity of a cellular component, such as RNA or protein, in response to an external variable. An increase of a cellular component is called upregulation.

An example of downregulation is the cellular decrease in the number of receptors to a molecule, such as a hormone or neurotransmitter, which reduces the cell's sensitivity to the molecule. This phenomenon is an example of a locally acting negative feedback mechanism.

An example of upregulation is the increased number of cytochrome P450 enzymes in liver cells when xenobiotic molecules such as dioxin are administered (resulting in greater degradation of these molecules).

Some receptor agonists may cause downregulation of their respective receptor(s), while most receptor antagonists may temporally upregulate their respective receptor(s). The disequilibrium caused by these changes often causes withdrawal when the long-term use of a medication or drug is discontinued. However, the use of certain receptor antagonists may also damage receptors faster than they upregulate (internalization of receptors due to antagonism).^{[citation needed]}

Upregulation and downregulation can also happen as a response to toxins or hormones. An example of upregulation in pregnancy is hormones that cause cells in the uterus to become more sensitive to oxytocin.

Receptor downregulation

Insulin receptor mechanism

The process of downregulation occurs when there are elevated levels of the hormone insulin in the blood. When insulin binds to its receptors on the surface of a cell, the hormone receptor complex undergoes endocytosis and is subsequently attacked by intracellular lysosomal enzymes. The internalization of the insulin molecules provides a pathway for degradation of the hormone as well as for regulation of the number of sites that are available for binding on the cell surface. At high plasma concentrations, the number of surface receptors for insulin is gradually reduced by the accelerated rate of receptor internalization and degradation brought about by increased hormonal binding. The rate of synthesis of new receptors within the endoplasmic reticulum and their insertion in the plasma membrane do not keep pace with their rate of destruction. Over time, this self-induced loss of target cell receptors for insulin reduces the target cell’s sensitivity to the elevated hormone concentration. The process of decreasing the number of receptor sites is virtually the same for all hormones; it varies only in the receptor hormone complex.

Cases

This process is illustrated by the insulin receptor sites on target cells in a person with type 2 diabetes. Due to the elevated levels of blood glucose in an overweight individual, the β-cells (islets of Langerhans) in the pancreas must release more insulin than normal to meet the demand and return the blood to homeostatic levels. The near-constant increase in blood insulin levels results from an effort to match the increase in blood glucose, which will cause receptor sites on the liver cells to downregulate and decrease the number of receptors for insulin, increasing the subject’s resistance by decreasing sensitivity to this hormone. There is also a hepatic decrease in sensitivity to insulin. This can be seen in the continuing gluconeogenesis in the liver even when blood glucose levels are elevated. This is the more common process of insulin resistance, which leads to adult-onset diabetes.

Another example can be seen in diabetes insipidus, in which the kidneys become insensitive to arginine vasopressin.

Reversal

The process of downregulation can be counteracted in the above example. A person with type 2 diabetes can increase their sensitivity to insulin through proper diet and regular exercise, resulting in weight loss; some individuals may even return to their pre-diabetic state by following such a regimen.

References

Sherwood, L. (2004). “Human Physiology From Cells to Systems, 5th Ed” (p. 680). Belmont, CA: Brooks/Cole-Thomson Learning

Wilmore, J., Costill, D. (2004). Physiology of Sport and Exercise, 3rd Ed (p. 164). Champaign, IL: Human Kinetics

External links

Down-Regulation at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 成人における迅速導入気管挿管のための神経筋遮断剤（NMBA） neuromuscular blocking agents nmba for rapid sequence intubation in adults
2. HIV感染における肺気腫様疾患 emphysema like disease in hiv infection
3. リウマチ性疾患における生物学的製剤の概要 overview of biologic agents in the rheumatic diseases
4. 降圧療法に伴う離脱症候群 withdrawal syndromes with antihypertensive therapy
5. 黒色腫（メラノーマ）の分子生物学 the molecular biology of melanoma

English Journal

Upregulation of Sirt1 in carbon-tetrachloride-induced acute liver injury.

Xie J, Wan J, Jiang R, Lu H, Peng X, Zhang L.SourceDepartment of Pathophysiology, Chongqing Medical University , Chongqing , China.
Drug and chemical toxicology.Drug Chem Toxicol.2013 Jul;36(3):277-83. doi: 10.3109/01480545.2012.710630. Epub 2012 Aug 31.
Sirtuin 1 (Sirt1) has been the focus of intense scrutiny because of its longevity activity. Recent studies also revealed the important role of Sirt1 in metabolic liver diseases. The present study was designed to elucidate the pathophysiological significance of Sirt1 in CCl(4)-induced acute liver inj
PMID 22934562

Hydroxytyrosyl ethyl ether exhibits stronger intestinal anticarcinogenic potency and effects on transcript profiles compared to hydroxytyrosol.

Pereira-Caro G, Mateos R, Traka MH, Bacon JR, Bongaerts R, Sarriá B, Bravo L, Kroon PA.SourceInstitute of Food Research, Norwich Research Park, Colney Lane, Norwich NR4 7UA, UK; IFAPA, Centro Venta del Llano, Road Bailén-Motril, Km 18.5, 23620 Mengibar (Jaén), Spain.
Food chemistry.Food Chem.2013 Jun 1;138(2-3):1172-82. doi: 10.1016/j.foodchem.2012.11.118. Epub 2012 Dec 5.
The anticarcinogenic activity of hydroxytyrosyl ethyl ether (HTy-Et) compared to its precursor hydroxytyrosol (HTy) has been studied in human Caco-2 colon adenocarcinoma cells. 451 and 977 genes were differentially expressed in Caco-2 cells exposed to HTy or HTy-Et for 24h, respectively, compared wi
PMID 23411228

Apple polyphenols suppress antigen presentation of ovalbumin by THP-1-derived dendritic cells.

Katayama S, Kukita T, Ishikawa E, Nakashima S, Masuda S, Kanda T, Akiyama H, Teshima R, Nakamura S.SourceDepartment of Bioscience and Biotechnology, Shinshu University, 8304 Minamiminowamura, Ina, Nagano 399-4598, Japan.
Food chemistry.Food Chem.2013 Jun 1;138(2-3):757-61. doi: 10.1016/j.foodchem.2012.10.076. Epub 2012 Nov 17.
Apple polyphenol extract (AP) and procyanidin contained in AP were investigated for their immunomodulatory effects using THP-1-derived human dendritic cells (TDDCs). The expression levels of HLA-DR (MHC class II) and CD86 (costimulatory molecule) were measured as an indicator of antigen presentation
PMID 23411172

Japanese Journal

GSK3β inhibition and LEF1 upregulation in skeletal muscle following a bout of downhill running

Amin Hiral,Vachris Judy,Hamilton Alicia [他]
The journal of physiological sciences 64(1), 1-11, 2014-01
NAID 40019937994

General Anesthetics Inhibit LPS-Induced IL-1β Expression in Glial Cells.

Tanaka Tomoharu,Kai Shinichi,Matsuyama Tomonori,Adachi Takehiko,Fukuda Kazuhiko,Hirota Kiichi
PloS one 8(12), 2013-12-11
… [Conclusions/Significance]Taken together, our results indicate that general anesthetics inhibit LPS-induced IL-1β upregulation in glial cells, particularly microglia, and affects HPA axis participation in the stress response. …
NAID 120005373082

CCL2/CCR2 augments the production of transforming growth factor-beta1, type 1 collagen and CCL2 by human CD45-/collagen 1-positive cells under high glucose concentrations

Hara Akinori,Sakai Norihiko,Furuichi Kengo,Sakai Yoshio,Takeya Motohiro,Bucala Richard,Mukaida Naofumi,Takuwa Yoh,Matsushima Kouji,Kaneko Shuichi,Wada Takashi
Clinical and Experimental Nephrology 17(6), 793-804, 2013-12
… In addition, preincubation of the cells with CCL2 enhanced the high glucose-induced upregulation of TGF-β1, pro-COL1A1 and CCL2 and migration of the cells, and this effect was partly inhibited by treatment with CCR2 inhibitors. …
NAID 120005368211