ER stress has been implicated in the pathogenesis of several human diseases. However, most studies in vivo or in human samples, have been based on tissues, after either induction of pathology in animals or in biopsy samples. It is interesting to speculate if ER stress can be measured in blood samples and whether it can e used as a clinical marker to assess the progression of disease (based on the activation of specific UPR/ ERAD/ apoptosis markers. Any insight into this subject is appreciated.
here are some nice papers : http://www.ncbi.nlm.nih.gov/pubmed/?term=ER+stress
Dear Khalid,
thanks for the papers but ROS and even protein oxidation measurements all are indirect measurements for the conditions which favour the activation of ER stress (Oxidative stress/hypoxia, Protein misfolding etc). But what about UPR signal sensors or apoptotic markers, specific to ER stress induced cell death (CHOP/ Caspase-12). I am curious to know if they can be measured in blood samples, which can be collected from diseased or healthy human subjects?
You should see the recognized literature to see if some one worked on it , i think Scopus database ca be usefull =D share the results with me im interested too =D good luck
Hi Kanika, it is a good thought. It is possible to Detect ER stress (UPR markers) in blood samples if the disease is in context with Blood cells. What I understand that ER stress is an adaptive process of cells and it is not just associated with only diseases but it is associated with physiological changes as well which are not related with disease. So, how will you correlate it with disease or physiological process even if you check it. Also, cell types are varying in different lines of ER stress pathways. I mean specific cell types induce specific branch of ER stress pathway. So i am just wondering how your purpose will be solved and what type of particular disease you are targeting.
Hi,
I echo what Mahendra says above. I am not aware of UPR markers in plasma or serum. The only way I think you can (sort of) get at that is to induce UPR in cultured cells and then perform proteomics on supernatants. Do this with and without various UPR modulators (chemical chaperones or salubrinal) or inducers (tunicamycin, thapisgargin) and compare, then you might have an idea of a secreted "UPR-ome". Again, this is likely cell type and UPR-inducer specific.
I think you can measure the GRP78 levels with an ELISA kit.
Another way to analyse ER stress, you can isolate the total RNA from samples (blood or tissue) and than synthesis cDNA. And you can determine the mRNA expressions of ER stress releated genes by using RT-PCR.
I study the role of the UPR in cancer progression. In cancerous cells GRP78 is translocated to the cell surface and is secreted in high levels by a number of solid tumours. Circulating GRP78 is known to recruit surrounding cell (tumour-associated macrophages and endothelial cells) to support spread into the microenvironment and has been proposed as a cancer biomarker.
http://www.ncbi.nlm.nih.gov/pubmed/17440054
As far as I am aware this is the only circulating biomarker of ER-stress as it predominately initiates intracellular responses.
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