User:Narvikvaren/sandbox
Sections I will add to and what I will add.
[edit]Endoplasmic reticulum stress in beta cells
[edit]Severe or prolonged episodes of ER stress can lead to the death of beta cells, which can contribute to the development of both type 1 and type 2 diabetes.
ER stress in beta cells links obesity to type 2 diabetes and inflammation to type 1 diabetes.
ER stress in peripheral cells has also been linked to insulin resistance[1], a precursor to type 2 diabetes.
ER Stress and Inflammation
[edit]All three of the pathways involved in the resolution of ER stress by the Unfolded Protein Response (UPR) are also related to inflammation[2]. The two pathways are very connected and both have been shown to activate each other[2]
Resolution of ER stress[edit]
[edit]Activation of ER stress by lipids results in a typical Unfolded Protein Response (UPR) to primarily restore ER function, whereas cytokine-activated ER stress leads to an atypical UPR that preferentially activate apoptosis in beta cells.[3][2]
The UPR is activated when GRP78, a.k.a. BiP, a protein-folding chaperone, is recruited to assist in protein folding. In ß-cells, insulin production is a major source of improperly folded protein[4]. GRP78 is normally bound to the luminal domain of ATF6, IRE1, and PERK, which prevents them from initiating their respective pathways of the UPR. When GRP78 is recruited to assist in protein folding, unbound ATF6, IRE1 and PERK are able to initiate the UPR.[5] The UPR is also activated by cytokines[6]
ER-stress activates Apoptosis through C/EBP Homologous Protein (CHOP)[7]
Measurement
[edit]ER Stress can be measured using Quantitative Real-Time RT-PCR to measure the rate at which XBP1 is cleaved by IRE1 when the UPR is activated.[8] XBP1 mRNA cleavage leads to the translation of a transcription factor for genes that resolve ER stress[9]. Measuring the rate at which XBP1 is cleaved gives a quantitative measure of ER stress in real time.
References[edit]
[edit]- ^ Wellen, Kathryn E.; Hotamisligil, Gökhan S. (2005-05-02). "Inflammation, stress, and diabetes". Journal of Clinical Investigation. 115 (5): 1111–1119. doi:10.1172/JCI25102. ISSN 0021-9738. PMC 1087185. PMID 15864338.
{{cite journal}}: CS1 maint: PMC format (link) - ^ a b c Hotamisligil, Gökhan S. (2010-03). "Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease". Cell. 140 (6): 900–917. doi:10.1016/j.cell.2010.02.034. ISSN 0092-8674. PMC 2887297. PMID 20303879.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Pirot P, Eizirik DL, Cardozo AK (2006) Interferon-gamma potentiates endoplasmic reticulum stress-induced death by reducing pancreatic beta cell defence mechanisms. Diabetologia 49:1229–1236
- ^ Eizirik DL, Cardozo AK, Cnop M (2008) The role for endoplasmic reticulum stress in diabetes mellitus. Endocr Rev 29:42-61
- ^ Wang, Miao; Kaufman, Randal J. (January 2016). "Protein misfolding in the endoplasmic reticulum as a conduit to human disease". Nature. 529 (7586): 326–335. doi:10.1038/nature17041. ISSN 0028-0836.
- ^ Hotamisligil, Gökhan S. (March 2010). "Endoplasmic Reticulum Stress and the Inflammatory Basis of Metabolic Disease". Cell. 140 (6): 900–917. doi:10.1016/j.cell.2010.02.034. ISSN 0092-8674. PMC 2887297. PMID 20303879.
- ^ Hu, Hai; Tian, Mingxing; Ding, Chan; Yu, Shengqing (2019-01-04). "The C/EBP Homologous Protein (CHOP) Transcription Factor Functions in Endoplasmic Reticulum Stress-Induced Apoptosis and Microbial Infection". Frontiers in Immunology. 9: 3083. doi:10.3389/fimmu.2018.03083. ISSN 1664-3224. PMC 6328441. PMID 30662442.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link) - ^ van Schadewijk, Annemarie; van’t Wout, Emily F. A.; Stolk, Jan; Hiemstra, Pieter S. (March 2012). "A quantitative method for detection of spliced X-box binding protein-1 (XBP1) mRNA as a measure of endoplasmic reticulum (ER) stress". Cell Stress and Chaperones. 17 (2): 275–279. doi:10.1007/s12192-011-0306-2. ISSN 1355-8145. PMC 3273559. PMID 22038282.
- ^ Wang, Miao; Kaufman, Randal J. (January 2016). "Protein misfolding in the endoplasmic reticulum as a conduit to human disease". Nature. 529 (7586): 326–335. doi:10.1038/nature17041. ISSN 0028-0836.