Endoplasmic Reticulum Chaperones GRP78 and Calreticulin Prevent Oxidative Stress, Ca2+ Disturbances, and Cell Death in Renal Epithelial Cells

Liu, Hong; Bowes, Russell C.; Water, Bob van de; Sillence, Christopher; Nagelkerke, J. Fred; Stevens, James

doi:10.1074/jbc.272.35.21751

Cited by 357 publications

(323 citation statements)

References 72 publications

Supporting

Mentioning

297

Contrasting

Unclassified

Order By: Relevance

“…TG, on the other hand, depletes the calcium pool of the ER. Both pathways activate GRP78, a chaperone protein (Gomer et al, 1991;Li et al, 1993) and can be blocked by overexpression of Bcl2 (He et al, 1996;Qi et al, 1997;Liu et al, 1997). We show here that Etk is able to protect LNCaP cells from apoptosis induced by either agent.…”

Section: Discussionsupporting

confidence: 48%

“…TG inhibits an ATP-gated calcium pump controlling the in¯ux of calcium from the cytosol to the endoplasmic reticulum (ER), thereby depleting the calcium pool of the ER and activating the apoptosis pathway . This process is accompanied by an induction of GRP78 expression and caspase activation, and cells can be rescued by overexpression of Bcl2 (Qi et al, 1997;Liu et al, 1997). Thus, although PDT and TG take di erent routes to initiate the apoptotic process, there is a converging of pathways in the downstream events of apoptosis.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells from apoptosis induced by photodynamic therapy or thapsigargin

Xue

Qiu

et al. 1999

Oncogene

View full text Add to dashboard Cite

Prostate carcinoma (PCA) is the most frequently diagnosed malignancy in American men. PCA at advanced stages can both proliferate abnormally and resist apoptosis. Among the many known signal transduction pathways, phosphatidylinositide-3'OH kinase (PI3-kinase) has been shown to play an important role in cell survival and resistance to apoptosis. In this study, we investigate the involvement of Etk/Bmx, a newly discovered tyrosine kinase that is a substrate of PI3-kinase, in protection of prostate cancer cells from apoptosis. Parental LNCaP cells and two derivative cell lines, one overexpressing wild type Etk (Etkwt) and the other expressing a dominant negative Etk (EtkDN), were used to study the function of Etk. The cells were treated with photodynamic therapy (PDT), a newly approved cancer treatment which employs a photosensitizer and visible light to produce an oxidative stress in cells, often leading to apoptosis. Our results indicate that PDT induces apoptosis in LNCaP cells, as measured by DNA fragmentation and by cleavage of poly(ADP-ribose) polymerase (PARP), and moreover, the extent of apoptosis was much reduced in Etkwt cells as compared to LNCaP or EtkDN cells. Assay of overall cell viability con®rmed that Etkwt cells were considerably less sensitive to PDT than were the parental LNCaP or EtkDN cells. Similar results were found in response to thapsigargin (TG). A speci®c inhibitor of PI3-kinase, LY294002, abolished Etk activity and markedly increased TG-induced PARP cleavage. The results suggest that Etk/Bmx is an e cient e ector of PI3-kinase and that the newly described PI3-kinase/Etk pathway is involved in the protection of prostate carcinoma cells from apoptosis in response to PDT or TG.

show abstract

Section: Discussionsupporting

confidence: 48%

Section: Introductionmentioning

confidence: 99%

Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells from apoptosis induced by photodynamic therapy or thapsigargin

Xue

Qiu

et al. 1999

Oncogene

View full text Add to dashboard Cite

show abstract

“…Previously, many papers have reported that the expression of GRP78 in cells suppresses apoptosis. 16,29 Therefore, induction of GRP78 by NSAIDs may be involved in protection of gastric mucosal cells from NSAID-induced apoptosis. We previously reported that geranylgeranylacetone, an inducer of cytosolic molecular chaperons (heat-shock proteins) and an antiulcer drug, protects gastric mucosal cells from apoptosis, resulting in suppression of gastric lesions.…”

Section: Discussionmentioning

confidence: 99%

“…Cells initially adapt to the accumulation of unfolded proteins by inducing ER-resident stress proteins (molecular chaperons) such as glucose-regulated protein (GRP) 78 and GRP94. [14][15][16][17] These proteins refold the unfolded proteins in an attempt to maintain homeostasis in the ER. However, if this adaptation does not prove sufficient, the apoptotic response is initiated, by both ATF6-and ATF4-dependent activation of C/ EBP homologous transcription factor (CHOP).…”

Section: Introductionmentioning

confidence: 99%

Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis

et al. 2004

View full text Add to dashboard Cite

Apoptosis induced by nonsteroidal anti-inflammatory drugs (NSAIDs) is involved not only in the production of NSAIDinduced gastric lesions but also in the antitumor activity of these drugs. The endoplasmic reticulum (ER) stress response is a cellular mechanism that aids in protecting the ER against ER stressors and is involved in ER stressor-induced apoptosis. Here, we examine the relationship between this response and NSAID-induced apoptosis in cultured guineapig gastric mucosal cells. Exposure of cells to indomethacin, a commonly used NSAID, induced GRP78 as well as CHOP, a transcription factor involved in apoptosis. Three factors that positively regulate CHOP expression (ATF6, ATF4 and XBP-1) were activated and/or induced by indomethacin. NSAIDs other than indomethacin (diclofenac, ibuprofen and celecoxib) also induced CHOP. Monitoring of the transcriptional activities of ATF6 and CHOP by luciferase assay revealed that both were stimulated in the presence of indomethacin. Furthermore, indomethacin-induced apoptosis was suppressed in cultured guinea-pig gastric mucosal cells by expression of the dominant-negative form of CHOP, or in peritoneal macrophages from CHOP-deficient mice. These results suggest that ER stress response-related proteins, particularly CHOP, are involved in NSAID-induced apoptosis.

show abstract

“…Moreover, since studies have shown that increased expression of ER stress proteins prevents Ca 2 ϩ depletion from the ER and protects against cellular damage and death (Lievremont et al 1997;Liu et al 1997Liu et al , 1998Yu et al 1999), it is possible that an elevation of these proteins in this subgroup of patients may have been an attempt to compen-sate for these neuropathologic changes in this patient group. Indeed, several recent studies are suggestive of cellular loss and glial changes in cortical regions of patients with MDD, which may be correlated with severity of illness (Ongur et al 1998;Rajkowska et al 1999).…”

Section: Discussionmentioning

confidence: 99%

Increased Temporal Cortex ER Stress Proteins in Depressed Subjects Who Died by Suicide

Bown

Wang

MacQueen

et al. 2000

Neuropsychopharmacology

View full text Add to dashboard Cite

Regulation of ER stress proteins, such as the 78-kilodalton glucose regulated protein (GRP78) by chronic treatment with mood stabilizing drugs suggests that this family of proteins may be involved in the pathophysiology of mood disorders. Indeed, increased levels of GRP78, GRP94, and calreticulin, a third member of the ERCurrent theories of the pathophysiology of mood disorders suggest that prolonged increases in glucocorticoid levels, likely the result of prolonged environmental stress, lead to biochemical changes in cortical and limbic neurons that leave individuals vulnerable to depression (Duman et al. 1997). A number of studies have found evidence of neuronal atrophy and loss of hippocampal neurons in response to stress (Magarinos et al. 1996;Uno et al. 1989;Sapolsky et al. 1985), and a report of reduced hippocampal volumes in elderly patients with histories of depression suggests that analogous processes may occur in individuals with depression (Sheline et al. 1996). Some models of mood disorders (Hyman and Nestler 1996; Post 1992) have attempted to incorporate the notion of compensatory processes into an understanding of the pathophysiologic changes that occur in patients with mood disorders, but few studies have tested these notions empirically (Post 1992). Part of the difficulty has been identifying neuroprotective mechanisms that may be of relevance for mood disorders.Recently, we found that treatment with the mood stabilizing drugs, valproate and carbamazepine, increased expression of the 78-kilodalton glucose-regulated protein (GRP78) . GRP78 is a member of the ER stress protein family that includes GRP94 and calreticulin, all of which function as Ca 2 ϩ binding proteins and molecular chaperones to assist in the regulation of protein folding (Gething 1997). These proteins have neuroprotective properties, are induced by seizures and ischemic damage, and may be involved in Alzheimer's disease pathology (Yu et al. 1999;Lowenstein et al. 1994;Hamos et al. 1991).Increased expression of ER stress proteins by mood stabilizing drugs suggest that these proteins may be in- METHODS Postmortem brain tissue was obtained from the StanleyFoundation Neuropathology Consortium (4 groups of n ϭ 15 age-and sex-matched subjects, i.e., subjects with bipolar disorder (BD), subjects with Major Depressive Disorder (MDD), subjects with schizophrenia (SCZ), and non-psychiatric, non-neurologic comparison subjects) (Johnston et al. 1997). Details on dissection and clinical characteristics have been previously published (Dowlatshahi et al. 1998(Dowlatshahi et al. , 1999. Briefly, all medical records for psychiatric cases were reviewed by two psychiatrists. Diagnosis was determined according to DSM-IV criteria. If there was disagreement about the diagnosis, a third psychiatrist read the records. If a diagnosis could not be established, a family member was then interviewed. All interviewed relatives were first degree except for two (one aunt and one father-in-law). Similarly, a clinical interview was performed with a family member...

show abstract

Endoplasmic Reticulum Chaperones GRP78 and Calreticulin Prevent Oxidative Stress, Ca2+ Disturbances, and Cell Death in Renal Epithelial Cells

Cited by 357 publications

References 72 publications

Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells from apoptosis induced by photodynamic therapy or thapsigargin

Etk/Bmx, a PH-domain containing tyrosine kinase, protects prostate cancer cells from apoptosis induced by photodynamic therapy or thapsigargin

Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosis

Increased Temporal Cortex ER Stress Proteins in Depressed Subjects Who Died by Suicide

Contact Info

Product

Resources

About