p53 activation inhibits ochratoxin A-induced apoptosis in monkey and human kidney epithelial cells via suppression of JNK activation

2011 ◽  
Vol 411 (2) ◽  
pp. 458-463 ◽  
Author(s):  
Jinghua Li ◽  
Shutao Yin ◽  
Yinhui Dong ◽  
Lihong Fan ◽  
Hongbo Hu
Keyword(s):  
Epithelial Cells ◽  
Ochratoxin A ◽  
Human Kidney ◽  
P53 Activation ◽  
Kidney Epithelial Cells ◽  
Induced Apoptosis ◽  
Jnk Activation

Nephritogenic ochratoxin A interferes with mitochondrial function and pH homeostasis in immortalized human kidney epithelial cells

2000 ◽  
Vol 440 (4) ◽  
pp. 521-529 ◽  
Author(s):  
Stefan Eder ◽  
Andreas Benesic ◽  
Ruth Freudinger ◽  
Judith Engert ◽  
Gerald Schwerdt ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ochratoxin A ◽  
Mitochondrial Function ◽  
Human Kidney ◽  
Ph Homeostasis ◽  
Kidney Epithelial Cells

Nephritogenic ochratoxin A interferes with mitochondrial function and pH homeostasis in immortalized human kidney epithelial cells

2000 ◽  
Vol 440 (4) ◽  
pp. 521 ◽  
Author(s):  
Stefan Eder ◽  
Andreas Benesic ◽  
Ruth Freudinger ◽  
Judith Engert ◽  
Gerald Schwerdt ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ochratoxin A ◽  
Mitochondrial Function ◽  
Human Kidney ◽  
Ph Homeostasis ◽  
Kidney Epithelial Cells

Prevention of TNF-α-induced apoptosis in polyamine-depleted IEC-6 cells is mediated through the activation of ERK1/2

2004 ◽  
Vol 286 (3) ◽  
pp. G479-G490 ◽  
Author(s):  
Sujoy Bhattacharya ◽  
Ramesh M. Ray ◽  
Leonard R. Johnson
Keyword(s):  
Epithelial Cells ◽  
Cytochrome C ◽  
Critical Role ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Cytochrome C Release ◽  
Erk Phosphorylation ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Jnk Activation

It has been documented that polyamines play a critical role in the regulation of apoptosis in intestinal epithelial cells. We have recently reported that protection from TNF-α/cycloheximide (CHX)-induced apoptosis in epithelial cells depleted of polyamines is mediated through the inactivation of a proapoptotic mediator, JNK. In this study, we addressed the involvement of the MAPK pathway in the regulation of apoptosis after polyamine depletion of IEC-6 cells. Polyamine depletion by α-difluromethylornithine (DFMO) resulted in the sustained activation of ERK in response to TNF-α/CHX treatment. Pretreatment of polyamine-depleted IEC-6 cells with a cell membrane-permeable MEK1/2 inhibitor, U-0126, significantly inhibited TNF-α/CHX-induced ERK phosphorylation and significantly increased DNA fragmentation, JNK activity, and caspase-3 activity in response to TNF-α/CHX. Moreover, the dose dependency of U-0126-mediated inhibition of TNF-α/ CHX-induced ERK phosphorylation correlated with the reversal of the antiapoptotic effect of DFMO. IEC-6 cells expressing constitutively active MEK1 had decreased TNF-α/CHX-induced JNK phosphorylation and were significantly protected from apoptosis. Conversely, a dominant-negative MEK1 resulted in high basal activation of JNK, cytochrome c release, and spontaneous apoptosis. Polyamine depletion of the dominant-negative MEK1 cells did not prevent JNK activation or cytochrome c release and failed to confer protection from both TNF-α/CHX and camptothecin-induced apoptosis. Finally, expression of a dominant-negative mutant of JNK significantly protected IEC-6 cells from TNF-α/CHX-induced apoptosis. These data indicate that polyamine depletion results in the activation of ERK, which inhibits JNK activation and protects cells from apoptosis.

scholarly journals Abrogation of ER stress-induced apoptosis of alveolar epithelial cells by angiotensin 1–7

2013 ◽  
Vol 305 (1) ◽  
pp. L33-L41 ◽  
Author(s):  
Bruce D. Uhal ◽  
Hang Nguyen ◽  
MyTrang Dang ◽  
Indiwari Gopallawa ◽  
Jing Jiang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Er Stress ◽  
Cathepsin D ◽  
Primary Cultures ◽  
A549 Cells ◽  
Surfactant Protein ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Induced Apoptosis ◽  
Jnk Activation

Earlier work showed that apoptosis of alveolar epithelial cells (AECs) in response to endogenous or xenobiotic factors is regulated by autocrine generation of angiotensin (ANG) II and its counterregulatory peptide ANG1–7. Mutations in surfactant protein C (SP-C) induce endoplasmic reticulum (ER) stress and apoptosis in AECs and cause lung fibrosis. This study tested the hypothesis that ER stress-induced apoptosis of AECs might also be regulated by the autocrine ANGII/ANG1–7 system of AECs. ER stress was induced in A549 cells or primary cultures of human AECs with the proteasome inhibitor MG132 or the SP-C BRICHOS domain mutant G100S. ER stress activated the ANGII-generating enzyme cathepsin D and simultaneously decreased the ANGII-degrading enzyme ACE-2, which normally generates the antiapoptotic peptide ANG1–7. TAPI-2, an inhibitor of ADAM17/TACE, significantly reduced both the activation of cathepsin D and the loss of ACE-2. Apoptosis of AECs induced by ER stress was measured by assays of mitochondrial function, JNK activation, caspase activation, and nuclear fragmentation. Apoptosis induced by either MG132 or the SP-C BRICHOS mutant G100S was significantly inhibited by the ANG receptor blocker saralasin and was completely abrogated by ANG1–7. Inhibition by ANG1–7 was blocked by the specific mas antagonist A779. These data show that ER stress-induced apoptosis is mediated by the autocrine ANGII/ANG1–7 system in human AECs and demonstrate effective blockade of SP-C mutation-induced apoptosis by ANG1–7. They also suggest that therapeutic strategies aimed at administering ANG1–7 or stimulating ACE-2 may hold potential for the management of ER stress-induced fibrotic lung disorders.

scholarly journals Identification of Noninvasive Biomarkers for Nephrotoxicity Using HK-2 Human Kidney Epithelial Cells

2014 ◽  
Vol 140 (2) ◽  
pp. 247-258 ◽  
Author(s):  
Sun Young Kim ◽  
So-Jung Sohn ◽  
A Jin Won ◽  
Hyung Sik Kim ◽  
Aree Moon
Keyword(s):  
Epithelial Cells ◽  
Human Kidney ◽  
Kidney Epithelial Cells ◽  
Noninvasive Biomarkers

Expression Profiling of Crystal-Induced Injury in Human Kidney Epithelial Cells

2006 ◽  
Vol 103 (1) ◽  
pp. p53-p62 ◽  
Author(s):  
Li Liang ◽  
Jianmin Chen ◽  
Ragini Vittal ◽  
Zachariah E. Selvanayagam ◽  
James A. McAteer ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Expression Profiling ◽  
Human Kidney ◽  
Kidney Epithelial Cells
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