EGFR-independent activation of p38 MAPK and EGFR-dependent activation of ERK1/2 are required for ROS-induced renal cell death

Dong, Jing; Ramachandiran, Sampath; Tikoo, Kulbhushan; Jia, Zhe; Lau, Serrine S.; Monks, Terrence J.

doi:10.1152/ajprenal.00132.2004

Cited by 88 publications

(73 citation statements)

References 44 publications

(54 reference statements)

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“…This remaining phosphorylation of Hsp27 might be due to MAPKAP kinase 2 activation occurring independent of p38. Indeed, SB203580 does not completely prevent stress-induced activation of MAPKAP-2 in LLC-PK1 cells (8). Alternatively, other protein kinases activated because of DCVC treatment could potentially phosphorylate Hsp27 (8).…”

Section: Discussionmentioning

confidence: 98%

“…Indeed, SB203580 does not completely prevent stress-induced activation of MAPKAP-2 in LLC-PK1 cells (8). Alternatively, other protein kinases activated because of DCVC treatment could potentially phosphorylate Hsp27 (8). This may also explain the effect observed by inhibition of JNK with SP600125, which resulted in decreased levels of phosphorylated p38 levels without affecting the stress-induced phosphorylation of Hsp27 (Fig.…”

Section: Discussionmentioning

confidence: 98%

“…Renal ischemia/reperfusion causes activation of JNK, p38, and ERK (4 -6), possibly as a direct consequence of oxidative stress (4,5). Also a variety of nephrotoxicants causes the activation of JNK and p38 (7)(8)(9). In vitro as well as in vivo studies using either antisense or pharmacological inhibitors suggest that sustained activation of JNK after PTC injury promotes cell death (5,10).…”

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confidence: 99%

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Heat Shock Protein 27 Is the Major Differentially Phosphorylated Protein Involved in Renal Epithelial Cellular Stress Response and Controls Focal Adhesion Organization and Apoptosis

Graauw

Tijdens

Cramer

et al. 2005

Journal of Biological Chemistry

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We used two-dimensional difference gel electrophoresis to determine early changes in the stress-response pathways that precede focal adhesion disorganization linked to the onset of apoptosis of renal epithelial cells. Treatment of LLC-PK1 cells with the model nephrotoxicant 1,2-(dichlorovinyl)-L-cysteine (DCVC) resulted in a >1.5-fold up-and down-regulation of 14 and 9 proteins, respectively, preceding the onset of apoptosis. Proteins included those involved in metabolism, i.e. aconitase and pyruvate dehydrogenase, and those related to stress responses and cytoskeletal reorganization, i.e. cofilin, Hsp27, and ␣-b-crystallin. The most prominent changes were found for Hsp27, which was related to a pI shift in association with an altered phosphorylation status of serine residue 82. Although both p38 and JNK were activated by DCVC, only inhibition of p38 with SB203580 reduced Hsp27 phosphorylation, which was associated with accelerated reorganization of focal adhesions, cell detachment, and apoptosis. In contrast, inhibition of JNK with SP600125 maintained cell adhesion as well as protection against apoptosis. Active JNK co-localized at focal adhesions after DCVC treatment in a FAK-dependent manner. Inhibition of active JNK localization at focal adhesions did not prevent DCVC-induced phosphorylation of Hsp27. Overexpression of a phosphorylationdefective mutant Hsp27 acted as a dominant negative and accelerated the DCVC-induced changes in the focal adhesions as well as the onset of apoptosis. Our data fit a model whereby early p38 activation results in a rapid phosphorylation of Hsp27, a requirement for proper maintenance of cell adhesion, thus suppressing renal epithelial cell apoptosis.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

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Heat Shock Protein 27 Is the Major Differentially Phosphorylated Protein Involved in Renal Epithelial Cellular Stress Response and Controls Focal Adhesion Organization and Apoptosis

Graauw

Tijdens

Cramer

et al. 2005

Journal of Biological Chemistry

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“…Several studies have shown that ROS leads to increases in the phosphorylation of ERK and p38 MAPK [26][27][28]. Cisplatin generates hydrogen peroxide (H 2 O 2 ), a relatively long-lived species of ROS, in a variety of cells including macrophages [29,30].…”

Section: Discussionmentioning

confidence: 99%

A Possible Mechanism of Cisplatin-Induced Tumor Necrosis Factor (TNF)-α Production in Murine Macrophages

Kim¹,

Yamamoto²,

Nakamura³

et al. 2013

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Cisplatin has been used for the treatment of various solid cancers or sarcomas; however, it can induce severe adverse effects. Among these adverse effects, nephrotoxicity, which has the potential to be a dose-limiting factor of this agent, develops due to the secretion of tumor necrosis factor-α (TNF-α) from macrophages; however, the precise mechanisms are still unclear. To elucidate possible mechanisms, we investigated the involvement of mitogen-activated protein kinases (MAPK) and reactive oxygen species (ROS) in cisplatin-induced TNF-α mRNA expression and protein production in the mouse macrophage-like cell line, RAW 264. Cisplatin (1 μM) significantly increased TNF-α mRNA expression and protein production. Extracellular-regulated kinase (ERK) and p38 MAPK, but not c-Jun N-terminal kinase (JNK), phosphorylation increased in response to cisplatin. Although an ERK inhibitor (PD98059) suppressed both cisplatin-induced TNF-α mRNA expression and its protein production, a p38 MAPK inhibitor (SB203580) decreased TNF-α protein production only. A JNK inhibitor (SP600125) had no effect on cisplatin-induced TNF-α mRNA expression. Furthermore, a scavenger of ROS, N,N'-dimethylthiourea, suppressed both ERK activation and TNF-α mRNA expression. These results suggest that the phosphorylation of ERK by ROS is involved in cisplatin-induced TNF-α mRNA expression and that the signaling pathway of p38 MAPK is related to TNF-α protein production.

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“…Cisplatin has multiple actions in cells, such as increasing ROS and MAPK signaling pathways (Dong et al, 2004;Koyama et al, 2011). To elucidate fenofibrate's mechanisms, inhibition of cisplatin-induced cytotoxicity via reduced of intracellular ROS was considered.…”

Section: Discussionmentioning

confidence: 99%

Fenofibrate reduces cisplatin-induced apoptosis of renal proximal tubular cells via inhibition of JNK and p38 pathways

et al. 2016

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-Cisplatin is widely used as a standard chemotherapy for solid tumors. The major adverse effect of cisplatin is nephrotoxicity in proximal tubular cells, via oxidative stress, DNA damage, cell apoptosis, and inflammation. The aim of this study was to investigate the pharmacological effect and mechanism of fibrate drugs on cisplatin-induced renal proximal tubular cell death. Cisplatin decreased cell viability of LLC-PK1 and HK-2 cells in a dose-dependent manner. Cisplatin-induced apoptosis was attenuated by co-treatment with fenofibrate while less so with clofibrate and bezafibrate. Fenofibrate's protective effect was not complimented by co-treatment with GW6471, a PPARα antagonist, indicating the protective effect occurred via a PPARα-independent mechanism. Treating cells with cisplatin induced reactive oxygen species (ROS), c-JUN N-terminal kinase (JNK), and p38 kinase (p38), but not extracellular signal-regulated kinase (ERK). Fenofibrate reversed cisplatin-induced JNK and p38 activation, but had no effect on ROS production. The findings suggest fenofibrate's protective effect on cisplatin-induced cytotoxicity is mediated by inhibition of JNK and p38. Moreover, fenofibrate did not alter cisplatin's antitumor effect on cancer cell lines including T84, SW-480, HepG2, and SK-LU-1 cells. Therefore, fenofibrate may be a candidate agent for further development as an adjuvant to cisplatin treatment.

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EGFR-independent activation of p38 MAPK and EGFR-dependent activation of ERK1/2 are required for ROS-induced renal cell death

Cited by 88 publications

References 44 publications

Heat Shock Protein 27 Is the Major Differentially Phosphorylated Protein Involved in Renal Epithelial Cellular Stress Response and Controls Focal Adhesion Organization and Apoptosis

Heat Shock Protein 27 Is the Major Differentially Phosphorylated Protein Involved in Renal Epithelial Cellular Stress Response and Controls Focal Adhesion Organization and Apoptosis

A Possible Mechanism of Cisplatin-Induced Tumor Necrosis Factor (TNF)-α Production in Murine Macrophages

Fenofibrate reduces cisplatin-induced apoptosis of renal proximal tubular cells via inhibition of JNK and p38 pathways

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