Direct involvement of the receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell death

Tsuruya, Kazuhiko; Ninomiya, Toshiharu; Tokumoto, Masanori; Hirakawa, Makoto; Masutani, Kohsuke; Taniguchi, Masatomo; Fukuda, Keisuke; Kanai, Hidetoshi; Kishihara, Kenji; Hirakata, Hideki; Iida, Mitsuo

doi:10.1046/j.1523-1755.2003.00709.x

Cited by 214 publications

(188 citation statements)

References 39 publications

Supporting

Mentioning

169

Contrasting

Unclassified

Order By: Relevance

“…Thus regulation of the expression of executioner caspases is crucial prior to the execution of cell death. Several studies including ours have previously demonstrated activation of executioner caspases (caspase-3/7 and -6) in both in vitro 12,13 and in vivo 14,15 models of cisplatin-induced AKI. Similarly, induction of p53 transcription factor was demonstrated in RTECs in both in vitro [16][17][18] and in vivo 19 studies of cisplatin AKI.…”

mentioning

confidence: 64%

“…Our previous study showed that the activity of caspase-1 is not increased in response to cisplatin in kidney cells. 12 Caspase-3 is predominately activated in a p53-dependent manner in cisplatin injury in RTECs 12,13 and in vivo in cisplatin nephrotoxicity but, like initiator caspases, it was not found to be a transcriptional target of p53. In fact, no p53-binding element was found in the caspase-3 gene.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Transcriptional activation of caspase-6 and -7 genes by cisplatin-induced p53 and its functional significance in cisplatin nephrotoxicity

et al. 2007

View full text Add to dashboard Cite

This study examined the role of cisplatin-induced p53 activation in regulation of caspases and cellular injury during cisplatin nephrotoxicity. The executioner caspase-6 and -7 but not caspase-3 were identified as transcriptional targets of p53 in cisplatin injury as revealed by chromatin immunoprecipitation, a reporter gene and electrophoretic mobility shift assays, and real-time PCR following overexpression and inhibition of p53. DNA binding by p53 involved the first introns of the human and mouse caspase-7 gene and the mouse caspase-6 gene. Studies in human kidney, breast, ovary, colon, and prostate tumor cell lines also validated these findings. Treatment of p53 (À/À) cells with cisplatin did not induce caspase-6 and -7 expression and subsequent activation. In caspase-3 (À/À) cells, inhibition of caspase-6 and -7 activations markedly prevented cisplatin-induced cell death.In an in vivo model of cisplatin nephrotoxicity inhibition of p53 activation by a p53 inhibitor suppressed transactivation of the caspase-6 and -7 genes and prevented renal failure. p53 (À/À) mice were resistant to cisplatin nephrotoxicity as assessed by renal function and histology. These studies provide first evidence for p53-dependent transcriptional control of the caspase-6 and -7 genes and its functional significance in cisplatin injury to renal cells and functional implication of cisplatin-induced p53 induction in vitro and in vivo in cisplatin nephrotoxicity.

show abstract

mentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Transcriptional activation of caspase-6 and -7 genes by cisplatin-induced p53 and its functional significance in cisplatin nephrotoxicity

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Depending on its concentration, cisplatin induces necrosis as well as apoptosis in these cells, leading to acute renal failure. Multiple signaling pathways are activated by cisplatin in renal tubular cells (Baliga et al, 1998;Megyesi et al, 1998;Shiraishi et al, 2000;Kaushal et al, 2001;Nowak, 2002;Park et al, 2002;Ramesh and Reeves, 2002;Liu and Baliga, 2003;Tsuruya et al, 2003;Arany et al, 2004;Li et al, 2004;Sheikh-Hamad et al, 2004;Yu et al, 2005); however, it is unclear how these signals are integrated to determine cell injury and death (Arany and Safirstein, 2003).…”

Section: Introductionmentioning

confidence: 99%

Regulation of PUMA-α by p53 in cisplatin-induced renal cell apoptosis

et al. 2006

View full text Add to dashboard Cite

“…1 In previous animal studies, we and others have demonstrated an important role for TNF-␣ in the pathogenesis of cisplatin-induced renal injury. [2][3][4][5][6] Inhibition of TNF-␣ production or action markedly reduced the nephrotoxicity of cisplatin. 2,3 Stimulation of TNF-␣ production in the kidney by cisplatin involved both a stabilization of TNF-␣ mRNA 7 and a p38 MAPK-dependent increase in TNF-␣ mRNA translation, 4 however, the upstream signals responsible for TNF-␣ production remain unclear.…”

mentioning

confidence: 99%

TLR4 Signaling Mediates Inflammation and Tissue Injury in Nephrotoxicity

Zhang

Ramesh

Uematsu

et al. 2008

Journal of the American Society of Nephrology

281

256

View full text Add to dashboard Cite

The molecular mechanisms of acute kidney injury (AKI) remain unclear. Toll-like receptors (TLRs), widely expressed on leukocytes and kidney epithelial cells, regulate innate and adaptive immune responses. The present study examined the role of TLR signaling in cisplatin-induced AKI. Cisplatin-treated wildtype mice had significantly more renal dysfunction, histologic damage, and leukocytes infiltrating the kidney than similarly treated mice with a targeted deletion of TLR4 [Tlr4(Ϫ/Ϫ)]. Levels of cytokines in serum, kidney, and urine were increased significantly in cisplatin-treated wild-type mice compared with saline-treated wild-type mice and cisplatin-treated Tlr4(Ϫ/Ϫ) mice. Activation of JNK and p38, which was associated with cisplatin-induced renal injury in wild-type mice, was significantly blunted in Tlr4(Ϫ/Ϫ) mice. Using bone marrow chimeric mice, it was determined that renal parenchymal TLR4, rather than myeloid TLR4, mediated the nephrotoxic effects of cisplatin. Therefore, activation of TLR4 on renal parenchymal cells may activate p38 MAPK pathways, leading to increased production of inflammatory cytokines, such as TNF-␣ and subsequent kidney injury. Targeting the TLR4 signaling pathways may be a feasible therapeutic strategy to prevent cisplatin-induced AKI in humans.

show abstract

Direct involvement of the receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell death

Abstract: Based on these data, we conclude that the Fas- and TNFR1-mediated apoptotic pathways are directly involved in the pathogenesis of cisplatin-induced RTC death process.

Cited by 214 publications

References 39 publications

Transcriptional activation of caspase-6 and -7 genes by cisplatin-induced p53 and its functional significance in cisplatin nephrotoxicity

Transcriptional activation of caspase-6 and -7 genes by cisplatin-induced p53 and its functional significance in cisplatin nephrotoxicity

Regulation of PUMA-α by p53 in cisplatin-induced renal cell apoptosis

TLR4 Signaling Mediates Inflammation and Tissue Injury in Nephrotoxicity

Contact Info

Product

Resources

About