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関連する概念動画

Hypoxia01:23

Hypoxia

2.0K
Hypoxia is a medical condition characterized by an inadequate oxygen supply to body tissues. It typically manifests as a bluish discoloration of the skin and mucosae, especially in fair-skinned individuals, when hemoglobin (Hb) saturation drops below 75%.
Types of Hypoxia
There are four primary types of hypoxia, each resulting from a different cause:
1. Anemic hypoxia: This type occurs due to insufficient oxygen delivery caused by a lack of red blood cells (RBCs) or RBCs with abnormal or...
2.0K
Transcription Factors02:16

Transcription Factors

82.3K
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
82.3K
Factors Affecting Solubility04:01

Factors Affecting Solubility

36.7K
Compared with pure water, the solubility of an ionic compound is less in aqueous solutions containing a common ion (one also produced by dissolution of the ionic compound). This is an example of a phenomenon known as the common ion effect, which is a consequence of the law of mass action that may be explained using Le Chȃtelier’s principle. Consider the dissolution of silver iodide:
36.7K
Transcription Elongation Factors02:35

Transcription Elongation Factors

13.5K
Transcription elongation is a dynamic process that alters depending upon the sequence heterogeneity of the DNA being transcribed. Hence, it is not surprising that the elongation complex's composition also varies along the way while transcribing a gene.
The transcription elongation is regulated via pausing of RNA polymerase on several occasions during transcription. In bacteria, these halts are necessary because the transcription of DNA into mRNA is coupled to the translation of that mRNA...
13.5K
Factors Affecting Drug Distribution: Miscellaneous Factors01:19

Factors Affecting Drug Distribution: Miscellaneous Factors

957
Drug distribution in the human body is a complex process influenced by various individual factors, including age, pregnancy, obesity, diet, body water composition, pH levels, and specific disease conditions.
Age plays a significant role due to differences in body composition among different age groups. Infants, for instance, have a higher proportion of total body water and lower albumin levels, a protein that binds drugs in the bloodstream. This unique composition in infants enhances the...
957
Electrolytes: van't Hoff Factor03:08

Electrolytes: van't Hoff Factor

36.4K
Colligative Properties of Electrolytes
The colligative properties of a solution depend only on the number, not on the identity, of solute species dissolved. The concentration terms in the equations for various colligative properties (freezing point depression, boiling point elevation, osmotic pressure) pertain to all solute species present in the solution. Nonelectrolytes dissolve physically without dissociation or any other accompanying process. Each molecule that dissolves yields one...
36.4K

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Author Spotlight: Improving Anesthesia Protocols for Enhanced Mouse Acupuncture Research
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低酸素誘導因子の構造的統合

Dalei Wu1, Nalini Potluri1, Jingping Lu1

  • 1Metabolic Disease Program, Sanford Burnham Prebys Medical Discovery Institute, Orlando, Florida 32827, USA.

Nature
|August 7, 2015
PubMed
まとめ

低酸素誘導因子 (HIF) は酸素不足に細胞の適応を調節し,腫瘍の成長を促します. HIF-α-ARNTヘテロダイマーに関する構造的な洞察は,小分子結合部位を詳細に記述することによって,抗がん薬の潜在的標的を明らかにする.

科学分野:

  • 生物化学
  • 分子生物学
  • 構造生物学

背景:

  • 低酸素誘導因子 (HIF) は,低酸素に対する細胞反応の重要な調節因子です.
  • HIFは,腫瘍の成長と進行に不可欠なプロセスであるエリトロポエーゼス,血管新生,代謝に関与する遺伝子を制御します.
  • HIFは,腫瘍形成における役割のために,魅力的な抗がん標的である.

研究 の 目的:

  • HIF-α-ARNT ヘテロディマー機能の構造的基礎を解明する.
  • HIFヘテロダイマーにおける潜在的小分子結合部位を特定し,標的がん治療を行う.
  • 低酸素反応要素 (HRE) の認識の構造的メカニズムを理解する.

主な方法:

  • マウスのHIF- 2α- ARNTとHIF- 1α- ARNTの異体体の構造を決定するために,X線結晶学を用いた.
  • 構造は小分子とDNA (低酸素反応要素) で複合的に解明された.
  • 小分子結合ポケットとDNA結合インターフェースの分析

主要な成果:

  • HIF-2α-ARNTとHIF-1α-ARNTの異体体の詳細な結晶構造が得られた.
  • 保存された四次構造が観察され,ARNTはHIF-αサブユニットの周りに渦巻く.

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Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice
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Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice

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Induction and Testing of Hypoxia in Cell Culture
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Induction and Testing of Hypoxia in Cell Culture

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Invasive Hemodynamic Assessment for the Right Ventricular System and Hypoxia-Induced Pulmonary Arterial Hypertension in Mice
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Induction and Testing of Hypoxia in Cell Culture
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Induction and Testing of Hypoxia in Cell Culture

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  • 5つの異なる小分子結合ポケットが特定され,PASドメインサイトとインターフェイス腔が含まれています.
  • DNA結合ヘッドとディスタルPASドメインは,効率的な低酸素反応要素認識のために協力します.
  • 癌に関連したHIF-α変異は,DNA結合とドメインの安定性に影響を与える機能的に重要な領域にマッピングされました.
  • 結論:

    • 構造データは,HIFヘテロジマー組立と機能のメカニズム的理解を提供します.
    • 特定された小分子結合部位は,HIFを標的とした新しい抗がん剤の開発の機会を提供します.
    • HIF-DNAの相互作用を理解することは,腫瘍性転写プログラムに障害を与える阻害剤の設計に不可欠です.