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research-review:fat-apoptosis-through-targeted-activation-of-caspase-8-a-new-mouse-model-of-inducible-and-reversible-lipoatrophy [2019/07/30 05:38] marcos |
research-review:fat-apoptosis-through-targeted-activation-of-caspase-8-a-new-mouse-model-of-inducible-and-reversible-lipoatrophy [2020/05/05 05:53] (current) marcos [Abstract] |
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The protein FKBPv is part of a [[https://en.wikipedia.org/wiki/Caspase |Caspase]]. Caspases are used to invoke [[https://en.wikipedia.org/wiki/Programmed_cell_death |programmed cell death]], a natural occurring phenomena. | The protein FKBPv is part of a [[https://en.wikipedia.org/wiki/Caspase |Caspase]]. Caspases are used to invoke [[https://en.wikipedia.org/wiki/Programmed_cell_death |programmed cell death]], a natural occurring phenomena. | ||
- | <hidden>[[https://en.wikipedia.org/wiki/Caspase |Caspases]] are [[https://www.britannica.com/science/proteolytic-enzyme |proteolytic enzymes]] (also called proteases or peptidases). Proteases are molecules that disassemble other molecules into smaller ones, a process called [[https://en.wikipedia.org/wiki/Catabolism |Catabolism]].</hidden> | + | <hidden Click to understand caspases.>[[https://en.wikipedia.org/wiki/Caspase |Caspases]] are [[https://www.britannica.com/science/proteolytic-enzyme |proteolytic enzymes]] (also called proteases or peptidases). Proteases are molecules that disassemble other molecules into smaller ones, a process called [[https://en.wikipedia.org/wiki/Catabolism |Catabolism]].</hidden> |
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- | Caspases are normally inactive, and need to be triggered. Caspases can be activated by the [[https://en.wikipedia.org/wiki/Caspase#Activation_of_caspases |removal of the prodomain]], in this case FKBPv. FKBPv does not normally [[https://en.wikipedia.org/wiki/Dimer_%28chemistry%29 |dimerize]], or join together in pairs, but can be caused to dimerize in the presence of an [[https://en.wikipedia.org/wiki/FK1012 |FK1012]] analog. Inactive Caspase pairs then merge in the process and begin to sever peptide bonds of the cell. | + | Caspase 8 exists in a cell as inactive pairs, and need to be triggered to become active. Caspases can be activated by the [[https://en.wikipedia.org/wiki/Caspase#Activation_of_caspases |removal of the prodomain]], in this case FKBPv. FKBPv does not normally [[https://en.wikipedia.org/wiki/Dimer_%28chemistry%29 |dimerize]], or join together in pairs, but can be caused to dimerize in the presence of an [[https://en.wikipedia.org/wiki/FK1012 |FK1012]] analog. Inactive Caspase pairs then merge in the process and begin to sever peptide bonds of the cell. |
Thus, the surface of the fat cells, having the FKBPv protein, can be dismantled using the dimerizing agent FK1012-analog. When this happens, the mouse loses fat cells and becomes a very lean mouse. Mice with the inducible fat loss were given the name FAT-ATTAC mice (fat apoptosis through targeted activation of caspase 8). | Thus, the surface of the fat cells, having the FKBPv protein, can be dismantled using the dimerizing agent FK1012-analog. When this happens, the mouse loses fat cells and becomes a very lean mouse. Mice with the inducible fat loss were given the name FAT-ATTAC mice (fat apoptosis through targeted activation of caspase 8). | ||
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==== Points of Interest ==== | ==== Points of Interest ==== | ||
- | * Cell death, or apoptosis, is a normal and desirable part of metabolism. For example, apoptosis helps clear tissues of cells that have degenerated and are performing poorly. Caspases, are normally involved in the execution of apoptosis ([[https://www.youtube.com/watch?v=-vmtK-bAC5E |see video]]). Researchers modified Caspase 8 to include the FKBPv protein. When the FKBPv protein is released from the caspase, it becomes an active [[https://en.wikipedia.org/wiki/Catabolism |catabolic]] [[https://en.wikipedia.org/wiki/Enzyme |enzyme]] and breaks down the fat cell. | + | * Cell death, or apoptosis, is a normal and desirable part of metabolism. For example, apoptosis helps clear tissues of cells that have degenerated and are performing poorly. Caspases, are normally involved in the execution of apoptosis ([[https://www.youtube.com/watch?v=-vmtK-bAC5E |see video]]). Researchers modified Caspase 8 to include the FKBPv protein. When the FKBPv protein is released from the caspase, the caspase becomes an active [[https://en.wikipedia.org/wiki/Catabolism |catabolic]] [[https://en.wikipedia.org/wiki/Enzyme |enzyme]] and breaks down the fat cell via the [[https://www.abeomics.com/caspase-cascade |caspase cascade]] |
* Life is largely made of proteins. Proteins are often made from [[http://kinemage.biochem.duke.edu/teaching/anatax/html/anatax.2i.html |subunits or domains]], that get reused in different types of proteins. Caspase 8, like all caspases, has subunits [[http://www.ebi.ac.uk/interpro/potm/2004_8/Page3.htm |p10 and p20]]. In its inactive state, caspases also have a [[https://www.sciencedirect.com/topics/neuroscience/caspase |prodomain]] such as FKBP. In the genetically modified mice, these subunits were fused with the modified FKBPv, which has a 1000 fold higher affinity for the dimerizing agent, FK1012-analog. | * Life is largely made of proteins. Proteins are often made from [[http://kinemage.biochem.duke.edu/teaching/anatax/html/anatax.2i.html |subunits or domains]], that get reused in different types of proteins. Caspase 8, like all caspases, has subunits [[http://www.ebi.ac.uk/interpro/potm/2004_8/Page3.htm |p10 and p20]]. In its inactive state, caspases also have a [[https://www.sciencedirect.com/topics/neuroscience/caspase |prodomain]] such as FKBP. In the genetically modified mice, these subunits were fused with the modified FKBPv, which has a 1000 fold higher affinity for the dimerizing agent, FK1012-analog. | ||
* After 2 weeks of administering the dimerizing agent, the blood stream showed near [[https://en.wikipedia.org/wiki/Gene_knockout |knockout]] levels of [[https://en.wikipedia.org/wiki/Cell_signaling |cell signaling]] proteins normally produced by fat cells, such as leptin and other [[https://en.wikipedia.org/wiki/Adipokine |adipokines]]. | * After 2 weeks of administering the dimerizing agent, the blood stream showed near [[https://en.wikipedia.org/wiki/Gene_knockout |knockout]] levels of [[https://en.wikipedia.org/wiki/Cell_signaling |cell signaling]] proteins normally produced by fat cells, such as leptin and other [[https://en.wikipedia.org/wiki/Adipokine |adipokines]]. |