Increased expression of the transient receptor potential melastatin 7 channel is critically involved in lipopolysaccharide-induced reactive oxygen species-mediated neuronal death

Felipe Nuñez-Villena, Alvaro Becerra, Cesar Echeverría, Nicolás Briceño, Omar Porras, Ricardo Armisén, Diego Varela, Ignacio Montorfano, Daniela Sarmiento, Felipe Simon

Resultado de la investigación: Article

36 Citas (Scopus)

Resumen

Aims: To assess the mechanisms involved in lipopolysaccharide (LPS)-induced neuronal cell death, we examined the cellular consequences of LPS exposure in differentiated PC12 neurons and primary hippocampal neurons. Results: Our data show that LPS is able to induce PC12 neuronal cell death without the participation of glial cells. Neuronal cell death was mediated by an increase in cellular reactive oxygen species (ROS) levels. Considering the prevalent role of specific ion channels in mediating the deleterious effect of ROS, we assessed their contribution to this process. Neurons exposed to LPS showed a significant intracellular Ca 2+ overload, and nonselective cationic channel blockers inhibited LPS-induced neuronal death. In particular, we observed that both LPS and hydrogen peroxide exposure strongly increased the expression of the transient receptor protein melastatin 7 (TRPM7), which is an ion channel directly implicated in neuronal cell death. Further, both LPS-induced TRPM7 overexpression and LPS-induced neuronal cell death were decreased with dithiothreitol, dipheniliodonium, and apocynin. Finally, knockdown of TRPM7 expression using small interference RNA technology protected primary hippocampal neurons and differentiated PC12 neurons from the LPS challenge. Innovation: This is the first report showing that TRPM7 is a key protein involved in neuronal death after LPS challenge. Conclusion: We conclude that LPS promotes an abnormal ROS-dependent TRPM7 overexpression, which plays a crucial role in pathologic events, thus leading to neuronal dysfunction and death.

Idioma originalEnglish
Páginas (desde-hasta)2425-2438
Número de páginas14
PublicaciónAntioxidants and Redox Signaling
Volumen15
N.º9
DOI
EstadoPublished - 1 nov 2011

Huella dactilar

Lipopolysaccharides
Reactive Oxygen Species
Cell death
Neurons
Cell Death
Proteins
Ion Channels
Dithiothreitol
PC12 Cells
RNA Interference
Neuroglia
Hydrogen Peroxide
Innovation
RNA
Technology

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Physiology
  • Clinical Biochemistry

Citar esto

Nuñez-Villena, Felipe ; Becerra, Alvaro ; Echeverría, Cesar ; Briceño, Nicolás ; Porras, Omar ; Armisén, Ricardo ; Varela, Diego ; Montorfano, Ignacio ; Sarmiento, Daniela ; Simon, Felipe. / Increased expression of the transient receptor potential melastatin 7 channel is critically involved in lipopolysaccharide-induced reactive oxygen species-mediated neuronal death. En: Antioxidants and Redox Signaling. 2011 ; Vol. 15, N.º 9. pp. 2425-2438.
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title = "Increased expression of the transient receptor potential melastatin 7 channel is critically involved in lipopolysaccharide-induced reactive oxygen species-mediated neuronal death",
abstract = "Aims: To assess the mechanisms involved in lipopolysaccharide (LPS)-induced neuronal cell death, we examined the cellular consequences of LPS exposure in differentiated PC12 neurons and primary hippocampal neurons. Results: Our data show that LPS is able to induce PC12 neuronal cell death without the participation of glial cells. Neuronal cell death was mediated by an increase in cellular reactive oxygen species (ROS) levels. Considering the prevalent role of specific ion channels in mediating the deleterious effect of ROS, we assessed their contribution to this process. Neurons exposed to LPS showed a significant intracellular Ca 2+ overload, and nonselective cationic channel blockers inhibited LPS-induced neuronal death. In particular, we observed that both LPS and hydrogen peroxide exposure strongly increased the expression of the transient receptor protein melastatin 7 (TRPM7), which is an ion channel directly implicated in neuronal cell death. Further, both LPS-induced TRPM7 overexpression and LPS-induced neuronal cell death were decreased with dithiothreitol, dipheniliodonium, and apocynin. Finally, knockdown of TRPM7 expression using small interference RNA technology protected primary hippocampal neurons and differentiated PC12 neurons from the LPS challenge. Innovation: This is the first report showing that TRPM7 is a key protein involved in neuronal death after LPS challenge. Conclusion: We conclude that LPS promotes an abnormal ROS-dependent TRPM7 overexpression, which plays a crucial role in pathologic events, thus leading to neuronal dysfunction and death.",
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Increased expression of the transient receptor potential melastatin 7 channel is critically involved in lipopolysaccharide-induced reactive oxygen species-mediated neuronal death. / Nuñez-Villena, Felipe; Becerra, Alvaro; Echeverría, Cesar; Briceño, Nicolás; Porras, Omar; Armisén, Ricardo; Varela, Diego; Montorfano, Ignacio; Sarmiento, Daniela; Simon, Felipe.

En: Antioxidants and Redox Signaling, Vol. 15, N.º 9, 01.11.2011, p. 2425-2438.

Resultado de la investigación: Article

TY - JOUR

T1 - Increased expression of the transient receptor potential melastatin 7 channel is critically involved in lipopolysaccharide-induced reactive oxygen species-mediated neuronal death

AU - Nuñez-Villena, Felipe

AU - Becerra, Alvaro

AU - Echeverría, Cesar

AU - Briceño, Nicolás

AU - Porras, Omar

AU - Armisén, Ricardo

AU - Varela, Diego

AU - Montorfano, Ignacio

AU - Sarmiento, Daniela

AU - Simon, Felipe

PY - 2011/11/1

Y1 - 2011/11/1

N2 - Aims: To assess the mechanisms involved in lipopolysaccharide (LPS)-induced neuronal cell death, we examined the cellular consequences of LPS exposure in differentiated PC12 neurons and primary hippocampal neurons. Results: Our data show that LPS is able to induce PC12 neuronal cell death without the participation of glial cells. Neuronal cell death was mediated by an increase in cellular reactive oxygen species (ROS) levels. Considering the prevalent role of specific ion channels in mediating the deleterious effect of ROS, we assessed their contribution to this process. Neurons exposed to LPS showed a significant intracellular Ca 2+ overload, and nonselective cationic channel blockers inhibited LPS-induced neuronal death. In particular, we observed that both LPS and hydrogen peroxide exposure strongly increased the expression of the transient receptor protein melastatin 7 (TRPM7), which is an ion channel directly implicated in neuronal cell death. Further, both LPS-induced TRPM7 overexpression and LPS-induced neuronal cell death were decreased with dithiothreitol, dipheniliodonium, and apocynin. Finally, knockdown of TRPM7 expression using small interference RNA technology protected primary hippocampal neurons and differentiated PC12 neurons from the LPS challenge. Innovation: This is the first report showing that TRPM7 is a key protein involved in neuronal death after LPS challenge. Conclusion: We conclude that LPS promotes an abnormal ROS-dependent TRPM7 overexpression, which plays a crucial role in pathologic events, thus leading to neuronal dysfunction and death.

AB - Aims: To assess the mechanisms involved in lipopolysaccharide (LPS)-induced neuronal cell death, we examined the cellular consequences of LPS exposure in differentiated PC12 neurons and primary hippocampal neurons. Results: Our data show that LPS is able to induce PC12 neuronal cell death without the participation of glial cells. Neuronal cell death was mediated by an increase in cellular reactive oxygen species (ROS) levels. Considering the prevalent role of specific ion channels in mediating the deleterious effect of ROS, we assessed their contribution to this process. Neurons exposed to LPS showed a significant intracellular Ca 2+ overload, and nonselective cationic channel blockers inhibited LPS-induced neuronal death. In particular, we observed that both LPS and hydrogen peroxide exposure strongly increased the expression of the transient receptor protein melastatin 7 (TRPM7), which is an ion channel directly implicated in neuronal cell death. Further, both LPS-induced TRPM7 overexpression and LPS-induced neuronal cell death were decreased with dithiothreitol, dipheniliodonium, and apocynin. Finally, knockdown of TRPM7 expression using small interference RNA technology protected primary hippocampal neurons and differentiated PC12 neurons from the LPS challenge. Innovation: This is the first report showing that TRPM7 is a key protein involved in neuronal death after LPS challenge. Conclusion: We conclude that LPS promotes an abnormal ROS-dependent TRPM7 overexpression, which plays a crucial role in pathologic events, thus leading to neuronal dysfunction and death.

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U2 - 10.1089/ars.2010.3825

DO - 10.1089/ars.2010.3825

M3 - Article

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AN - SCOPUS:79960557551

VL - 15

SP - 2425

EP - 2438

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

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ER -