Downregulation and upregulation
This article includes a list of general references, but it lacks sufficient corresponding inline citations. (August 2009) |
In
An example of downregulation is the cellular decrease in the expression of a specific receptor in response to its increased activation by a molecule, such as a hormone or neurotransmitter, which reduces the cell's sensitivity to the molecule. This is an example of a locally acting (negative feedback) mechanism.
An example of upregulation is the response of liver cells exposed to such xenobiotic molecules as dioxin. In this situation, the cells increase their production of cytochrome P450 enzymes, which in turn increases degradation of these dioxin molecules.
Downregulation or upregulation of an RNA or protein may also arise by an epigenetic alteration. Such an epigenetic alteration can cause expression of the RNA or protein to no longer respond to an external stimulus. This occurs, for instance, during drug addiction or progression to cancer.
Downregulation and upregulation of receptors
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All living cells have the ability to receive and process signals that originate outside their membranes, which they do by means of proteins called
Receptors are created, or expressed, from instructions in the DNA of the cell, and they can be increased, or upregulated, when the signal is weak, or decreased, or downregulated, when it is strong.[2] Their level can also be up or down regulated by modulation of systems that degrade receptors when they are no longer required by the cell.
Downregulation of receptors can also occur when receptors have been chronically exposed to an excessive amount of a ligand, either from endogenous mediators or from exogenous drugs. This results in ligand-induced desensitization or internalization of that receptor. This is typically seen in animal hormone receptors. Upregulation of receptors, on the other hand, can result in super-sensitized cells, especially after repeated exposure to an antagonistic drug or prolonged absence of the ligand.
Some
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.
Example: Insulin receptor downregulation
Elevated levels of the hormone
This process is illustrated by the
Another example can be seen in
Drug addiction
Family-based, adoption, and twin studies have indicated that there is a strong (50%) heritable component to vulnerability to substance abuse addiction.[10]
Especially among genetically vulnerable individuals, repeated exposure to a drug of abuse in adolescence or adulthood causes addiction by inducing stable downregulation or upregulation in expression of specific genes and microRNAs through epigenetic alterations.[11] Such downregulation or upregulation has been shown to occur in the brain's reward regions, such as the nucleus accumbens.[11] (See, for example, Epigenetics of cocaine addiction.)
Cancer
DNA damage appears to be the primary underlying cause of cancer.
As described in
Epigenetic upregulation of the DNA repair genes
See also
References
- PMID 24688749.
- ^ "Explain To Me: Receptor Upregulation/Downregulation". Retrieved 7 January 2017.
- ^ "On the Mechanism of Ligand-induced Down-Regulation of Insulin Receptor Level in the Liver Cel". The Journal of Biological Chemistry. 256.
- PMID 10930460.
- PMID 7821727.
- ^ ISBN 978-1133709510.
- PMID 19041393.
- PMID 16278749.
- ^ "Protein Controversies in Diabetes". journal.diabetes.org. Retrieved 2016-11-20.
- )
- ^ PMID 23643695.
- PMID 18403632.
- ISBN 978-953-51-1114-6.
- PMID 18704159.
- PMID 17616978.
- PMID 18704159.
Taken together, our data suggest that normal repair of a DNA break can occasionally cause heritable silencing of a CpG island–containing promoter by recruitment of proteins involved in silencing...This finding suggests that DNA damage may directly contribute to the large number of epigenetically silenced genes in tumors.
- PMID 17616978.
...data support a mechanistic link between HR and DNA methylation and suggest that DNA methylation in eukaryotes marks homologous recombined segments.
- PMID 25949794.
- PMID 24790823.
- PMID 25828893.
- S2CID 1830505.
- S2CID 535704.
- PMID 11956622.
- PMID 20972458.
Sources
- 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 U.S. National Library of Medicine Medical Subject Headings (MeSH)