scholarly journals Targeting Free Light Chain (FLC) Secretion and the Unfolded Protein Response in Myeloma Cells Using Van, a Combination of Repurposed Drugs

2018 ◽  
Vol 64 ◽  
pp. S74-S75
Author(s):  
Yao Jiang ◽  
Jennifer Down ◽  
Suzanne Raffles ◽  
Emma Jenkins ◽  
Lauren Ferretti ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Light Chain ◽  
Free Light Chain ◽  
Myeloma Cells ◽  
Unfolded Protein ◽  
Repurposed Drugs ◽  
The Unfolded Protein Response ◽  
Protein Response

Requirement of clusterin expression for prosurvival autophagy in hypoxic kidney tubular epithelial cells

2016 ◽  
Vol 310 (2) ◽  
pp. F160-F173 ◽  
Author(s):  
Hatem A. Alnasser ◽  
Qiunong Guan ◽  
Fan Zhang ◽  
Martin E. Gleave ◽  
Christopher Y. C. Nguan ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Light Chain ◽  
Fluorescent Protein ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Flow Cytometric Analysis ◽  
Kidney Cells ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Cellular autophagy is a prosurvival mechanism in the kidney against ischemia-reperfusion injury (IRI), but the molecular pathways that activate the autophagy in ischemic kidneys are not fully understood. Clusterin (CLU) is a chaperone-like protein, and its expression is associated with kidney resistance to IRI. The present study investigated the role of CLU in prosurvival autophagy in the kidney. Renal IRI was induced in mice by clamping renal pedicles at 32°C for 45 min. Hypoxia in renal tubular epithelial cell (TEC) cultures was induced by exposure to a 1% O2 atmosphere. Autophagy was determined by either light chain 3-BII expression with Western blot analysis or light chain 3-green fluorescent protein aggregation with confocal microscopy. Cell apoptosis was determined by flow cytometric analysis. The unfolded protein response was determined by PCR array. Here, we showed that autophagy was significantly activated by IRI in wild-type (WT) but not CLU-deficient kidneys. Similarly, autophagy was activated by hypoxia in human proximal TECs (HKC-8) and WT mouse primary TECs but was impaired in CLU-null TECs. Hypoxia-activated autophagy was CLU dependent and positively correlated with cell survival, and inhibition of autophagy significantly promoted cell death in both HKC-8 and mouse WT/CLU-expressing TECs but not in CLU-null TECs. Further experiments showed that CLU-dependent prosurvival autophagy was associated with activation of the unfolded protein response in hypoxic kidney cells. In conclusion, these data suggest that activation of prosurvival autophagy by hypoxia in kidney cells requires CLU expression and may be a key cytoprotective mechanism of CLU in the protection of the kidney from hypoxia/ischemia-mediated injury.

Activation of the Unfolded Protein Response in Acute Leukemia and Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4348-4348
Author(s):  
Toshiaki Yujiri ◽  
Atsuko Tanimura ◽  
Kozo Tagami ◽  
Yukinori Nakamura ◽  
Yukio Tanizawa
Keyword(s):  
Multiple Myeloma ◽  
Acute Leukemia ◽  
Unfolded Protein Response ◽  
Hematological Malignancies ◽  
Hodgkin's Lymphoma ◽  
Myeloma Cells ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

Abstract Accumulation of unfolded or misfolded proteins within the endoplasmic reticulum triggers the unfolded protein response (UPR). Evidence from several studies suggests that the UPR is activated in various tumors and might play a crucial role in tumor growth. For example, in vitro activation of the UPR alters the sensitivity of tumor cells to chemotherapeutic agents. The role of the UPR in hematological malignancies remains unclear, however. We therefore used real-time RT-PCR to quantitatively assess expression of UPR-related genes in clinical samples [peripheral blood (PB), bone marrow (BM) and lymph node (LN)] from 9 newly diagnosed patients with acute myeloid leukemia (AML), 5 with acute lymphoid leukemia (ALL), 4 with multiple myeloma (MM), 12 with Non-Hodgkin’s lymphoma, 1 with Hodgkin’s lymphoma and 6 with infectious lymphadenopathy. Thirteen healthy controls were also examined. Evaluated was the mRNA expression of a spliced form of X-box DNA-binding protein (XBP1), ER degradation enhancing a-mannosidase-like protein (EDEM), C/EBP-homologous protein (CHOP) and glucose regulated protein 78 (GRP78). We found the transcription levels of all four of these genes to be significantly higher in leukemic blast cells and myeloma cells than in control BM cells or PB mononuclear cells. In particular, leukemic cells from Philadelphia chromosome-positive ALL and aggressive MM cells showed higher levels of UPR-related gene expression. Thus, activation of the UPR might be associated with the malignant characteristics of leukemia and myeloma. By contrast, expression of UPR-related genes was not increased in lymphoma cells compared to LN cells from the patients with infectious lymphadenopathy. The present study provides the first evidence that UPR-related genes are activated in acute leukemia and multiple myeloma cells. Thus, activation of the UPR might play an important role in the development and progression of some hematological malignancies. More comprehensive in vitro studies will be necessary to determine the magnitude of the role played by the UPR, to identify the most important components of the pathway, and to determine which stages of tumor development are regulated by the UPR.

scholarly journals The unfolded protein response in bortezomib resistant myeloma cells

Pathology ◽  
2016 ◽  
Vol 48 ◽  
pp. S73-S74
Author(s):  
Nicholas Nikesitch ◽  
Chang Tao ◽  
Ken Lai ◽  
Murray Killingsworth ◽  
Sunna Bae ◽  
...  
Keyword(s):  
Unfolded Protein Response ◽  
Myeloma Cells ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response

scholarly journals Novel tropolones induce the unfolded protein response pathway and apoptosis in multiple myeloma cells

Oncotarget ◽  
2017 ◽  
Vol 8 (44) ◽  
pp. 76085-76098 ◽  
Author(s):  
Staci L. Haney ◽  
Cheryl Allen ◽  
Michelle L. Varney ◽  
Kaitlyn M. Dykstra ◽  
Eric R. Falcone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Unfolded Protein Response ◽  
Myeloma Cells ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response
Sign in / Sign up

Export Citation Format

Share Document