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What are Second Messengers?

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Because many receptor binding ligands are hydrophilic, they do not cross the cell membrane and thus their message must be relayed to a second messenger on the inside. There are several second messenger pathways, each with their own way of relaying information. G-protein coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol path is active when the receptor induces phospholipase C to hydrolyze the phospholipid,...
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Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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Water-soluble hormones cannot cross the plasma membrane, so they rely on protein receptors that span the membrane to trigger intracellular signaling pathways. These pathways then activate second messengers inside the cell, including cAMP or calcium ions.
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Hormones—or any molecule that binds to a receptor, known as a ligand—that are lipid-insoluble (water-soluble) are not able to diffuse across the cell membrane. In order to be able to affect a cell without entering it, these hormones bind to receptors on the cell membrane. When a first messenger, a hormone, binds to a receptor, a signal cascade is set off, causing second messengers, proteins inside the cell, to become activated, resulting in downstream effects.
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Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
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Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick.  Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
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Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test OGTT and Insulin Tolerance Test ITT
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Messengers of tolerance.

Sai Vineela Bontha1, Angela Fernandez-Piñeros1, Daniel G Maluf2

  • 1Translational Genomics and Transplant Laboratory, Department of Surgery, University of Virginia, Charlottesville 22903, United States.

Human Immunology
|February 7, 2018
PubMed
Summary

Organ transplant patients achieving operational tolerance without immunosuppressants offer insights into graft survival. Studying these individuals can reveal biomarkers and pathways to improve long-term outcomes for all transplant recipients.

Keywords:
Gene expressionInduced toleranceMeta-analysisMolecular biomarkersSolid organ transplant tolerance

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Area of Science:

  • Immunology
  • Transplantation Medicine
  • Genomics

Background:

  • Immunosuppressant drugs improve short-term organ transplant success but pose challenges like toxicity and limited long-term survival.
  • Operational tolerance, where patients maintain grafts without immunosuppressants, presents a rare but valuable model for study.
  • Understanding tolerance mechanisms is crucial for reducing immunosuppression and enhancing long-term allograft function.

Purpose of the Study:

  • To review gene expression studies in tolerant transplant patients.
  • To identify key genes and molecular pathways associated with operational tolerance.
  • To highlight research gaps in understanding and inducing transplant tolerance.

Main Methods:

  • Systematic review of gene expression studies in solid organ transplant recipients with operational tolerance.
  • Analysis of identified genes and molecular pathways linked to graft tolerance.
  • Compilation of current research on tolerant transplant populations.

Main Results:

  • Identification of specific genes and molecular pathways implicated in operational transplant tolerance.
  • Evidence suggesting that gene expression patterns in tolerant individuals differ significantly.
  • Highlighting the potential of biomarkers for tailoring immunosuppression and identifying tolerant patients.

Conclusions:

  • Gene expression studies in tolerant transplant patients provide critical insights into mechanisms of graft acceptance.
  • Further research is needed to translate these findings into clinical applications for broader transplant populations.
  • Leveraging knowledge from tolerant patients can significantly improve long-term organ transplant outcomes and reduce immunosuppression-related complications.