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

Research output: Contribution to journalArticlepeer-review

44 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2425-2438
Number of pages14
JournalAntioxidants and Redox Signaling
Volume15
Issue number9
DOIs
Publication statusPublished - 1 Nov 2011

ASJC Scopus subject areas

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

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