Role of MAPKs in platinum-induced neuronal apoptosis

被引：103

作者：

Scuteri, Arianna ^{[1
]}

Galimberti, Alessia ^{[1
]}

Maggioni, Daniele ^{[1
]}

Ravasi, Maddalena ^{[1
]}

Pasini, Silvia ^{[1
]}

Nicolini, Gabriella ^{[1
]}

Bossi, Mario ^{[1
]}

Miloso, Mariarosaria ^{[1
]}

Cavaletti, Guido ^{[1
]}

Tredici, Giovanni ^{[1
]}

机构：

[1] Univ Milano Bicocca, Dipartimento Neurosci & Tecnol Biomed, I-20052 Monza, Italy

来源：

NEUROTOXICOLOGY | 2009年 / 30卷 / 02期

关键词：

Dorsal root Ganglion neurons; Cisplatin; Oxaliplatin; MAPK; Neuronal toxicity; ACTIVATED PROTEIN-KINASES; CISPLATIN-INDUCED APOPTOSIS; SIGNAL-REGULATING KINASE; ROOT GANGLION NEURONS; DIABETIC-NEUROPATHY; NEURITE OUTGROWTH; C-JUN; INHIBITION; CELLS; ERK;

D O I：

10.1016/j.neuro.2009.01.003

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

An unsolved question is how platinum derivatives used for solid cancer therapy cause peripheral neuropathy in patients and apoptosis in "in vitro" models of chemotherapy-induced peripheral neuropathy. DRG neurons from E15 rat embryos were treated with toxic doses of oxaliplatin or cisplatin. Here, the role of MAPKs in neuronal apoptosis was studied. Both oxaliplatin and cisplatin induced a close-dependent neuronal apoptosis, modulated by the proteins of Bcl-2 family. Regarding MAPKs, platinum derivatives activated p38 while they reduced the active form and the total amount of JNK/Sapk. Both oxaliplatin and cisplatin activated ERKs at early stages, although they behaved differently at later stages. By using specific inhibitors of the various MAPKs it was demonstrated that the platinum-induced neuronal apoptosis is mediated by early p38 and ERK1/2 activation, while JNK/Sapk has a neuroprotective role. These results suggest a role for the different MAPKs in peripheral neuropathies characterized by apoptosis of DRG neurons. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：312 / 319

页数：8

共 54 条

[1]

Ahn NG, 2001, METHOD ENZYMOL, V332, P417

[2] SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase [J].

Bennett, BL ;

Sasaki, DT ;

Murray, BW ;

O'Leary, EC ;

Sakata, ST ;

Xu, WM ;

Leisten, JC ;

Motiwala, A ;

Pierce, S ;

Satoh, Y ;

Bhagwat, SS ;

Manning, AM ;

Anderson, DW .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (24) :13681-13686

[3] Effects of different schedules of oxaliplatin treatment on the peripheral nervous system of the rat [J].

Cavaletti, G ;

Tredici, G ;

Petruccioli, MG ;

Dondè, E ;

Tredici, P ;

Marmiroli, P ;

Minoia, C ;

Ronchi, A ;

Bayssas, M ;

Etienne, GG .

EUROPEAN JOURNAL OF CANCER, 2001, 37 (18) :2457-2463

[4] Emerging role of mitogen-activated protein kinases in peripheral neuropathies [J].

Cavaletti, Guido ;

Miloso, Mariarosaria ;

Nicolini, Gabriella ;

Scuteri, Arianna ;

Tredici, Giovanni .

JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, 2007, 12 (03) :175-194

[5] Role of ERK activation in cisplatin-induced apoptosis in A172 human glioma cells [J].

Choi, BK ;

Choi, CH ;

Oh, HL ;

Kim, YK .

NEUROTOXICOLOGY, 2004, 25 (06) :915-924

[6] ERK/MAPK regulates hippocampal histone phosphorylation following contextual fear conditioning [J].

Chwang, Wilson B. ;

O'Riordan, Kenneth J. ;

Levenson, Jonathan M. ;

Sweatt, J. David .

LEARNING & MEMORY, 2006, 13 (03) :322-328

[7]

Coffey ET, 2000, J NEUROSCI, V20, P7602

[8] Chronic activation of ERK and neurodegenerative diseases [J].

Colucci-D'Amato, L ;

Perrone-Capano, C ;

di Porzio, U .

BIOESSAYS, 2003, 25 (11) :1085-1095

[9] SB-203580 IS A SPECIFIC INHIBITOR OF A MAP KINASE HOMOLOG WHICH IS STIMULATED BY CELLULAR STRESSES AND INTERLEUKIN-1 [J].

CUENDA, A ;

ROUSE, J ;

DOZA, YN ;

MEIER, R ;

COHEN, P ;

GALLAGHER, TF ;

YOUNG, PR ;

LEE, JC .

FEBS LETTERS, 1995, 364 (02) :229-233

[10] THE BCL-2 FAMILY OF PROTEINS, AND THE REGULATION OF NEURONAL SURVIVAL [J].

DAVIES, AM .

TRENDS IN NEUROSCIENCES, 1995, 18 (08) :355-358

← 1 2 3 4 5 6 →