Glial inflammation and neurodegeneration induced by candoxin, a novel neurotoxin from Bungarus candidus venom: Global gene expression analysis using microarray

A. Pachiappan, M. M. Thwin, J. Manikandan, P. Gopalakrishnakone

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Candoxin (PDB #1JGK), a three-finger neurotoxin from Bungarus candidus venom, inhibits post-synaptic neuromuscular and neuronal α7nACh-receptors, and induces delayed cell-death throughout the glial population. When applied to cultured human glial cell lines, candoxin (CDX) induced cell death in a concentration (EC50∼1 μM) and time dependent manner. Results of TUNEL-histochemistry further confirm CDX-induced brain (hippocampus, frontal cortex, and temporal regions) damage when administered intracerebroventricularly (i.c.v) in adult mice. In this study, we explored differential gene expression profiles following exposure of human glial (Hs 683) cell lines to CDX at various time intervals using Affymetrix-GeneChips. By means of MAS and GeneSpring analyses, 105 genes whose expression was significantly (P<0.01) altered by at least 3-fold were selected. Results of the genome analysis reveal that the potential role of CDX at molecular level involves the regulation of genes in signal transduction, ubiquitin-inflammation, mitochondrial-dysfunction, and damage-response pathways. In addition, using QRT-PCR and rationally designed specific CDX-binding peptide (P-NT.II), we identified the genes - IL7R, IL13RA2, IL-1β, TNFRSF12A, GADD45A, CD44 and IFI44 - that might play an important role in CDX-induced glial inflammation, DNA-damage and degeneration. These findings reveal new insight into the molecular mechanisms of glial-driven neurodegeneration after exposure to neurotoxins.

Original languageEnglish (US)
Pages (from-to)883-899
Number of pages17
JournalToxicon
Volume46
Issue number8
DOIs
StatePublished - Dec 15 2005
Externally publishedYes

Fingerprint

Bungarus
Venoms
Neurotoxins
Microarray Analysis
Microarrays
Gene expression
Neuroglia
Inflammation
Gene Expression
Genes
Cell death
Cell Death
Cell Line
Signal transduction
In Situ Nick-End Labeling
Frontal Lobe
Temporal Lobe
Ubiquitin
candoxin
Interleukin-1

Keywords

  • Glial-degeneration and real-time PCR
  • Inflammation
  • Microarray
  • TUNEL-assay
  • Three-finger toxins

ASJC Scopus subject areas

  • Toxicology

Cite this

Glial inflammation and neurodegeneration induced by candoxin, a novel neurotoxin from Bungarus candidus venom : Global gene expression analysis using microarray. / Pachiappan, A.; Thwin, M. M.; Manikandan, J.; Gopalakrishnakone, P.

In: Toxicon, Vol. 46, No. 8, 15.12.2005, p. 883-899.

Research output: Contribution to journalArticle

@article{65b5ee3afa314cb58cf613540ab8ab1f,
title = "Glial inflammation and neurodegeneration induced by candoxin, a novel neurotoxin from Bungarus candidus venom: Global gene expression analysis using microarray",
abstract = "Candoxin (PDB #1JGK), a three-finger neurotoxin from Bungarus candidus venom, inhibits post-synaptic neuromuscular and neuronal α7nACh-receptors, and induces delayed cell-death throughout the glial population. When applied to cultured human glial cell lines, candoxin (CDX) induced cell death in a concentration (EC50∼1 μM) and time dependent manner. Results of TUNEL-histochemistry further confirm CDX-induced brain (hippocampus, frontal cortex, and temporal regions) damage when administered intracerebroventricularly (i.c.v) in adult mice. In this study, we explored differential gene expression profiles following exposure of human glial (Hs 683) cell lines to CDX at various time intervals using Affymetrix-GeneChips. By means of MAS and GeneSpring analyses, 105 genes whose expression was significantly (P<0.01) altered by at least 3-fold were selected. Results of the genome analysis reveal that the potential role of CDX at molecular level involves the regulation of genes in signal transduction, ubiquitin-inflammation, mitochondrial-dysfunction, and damage-response pathways. In addition, using QRT-PCR and rationally designed specific CDX-binding peptide (P-NT.II), we identified the genes - IL7R, IL13RA2, IL-1β, TNFRSF12A, GADD45A, CD44 and IFI44 - that might play an important role in CDX-induced glial inflammation, DNA-damage and degeneration. These findings reveal new insight into the molecular mechanisms of glial-driven neurodegeneration after exposure to neurotoxins.",
keywords = "Glial-degeneration and real-time PCR, Inflammation, Microarray, TUNEL-assay, Three-finger toxins",
author = "A. Pachiappan and Thwin, {M. M.} and J. Manikandan and P. Gopalakrishnakone",
year = "2005",
month = "12",
day = "15",
doi = "10.1016/j.toxicon.2005.08.017",
language = "English (US)",
volume = "46",
pages = "883--899",
journal = "Toxicon",
issn = "0041-0101",
publisher = "Elsevier Limited",
number = "8",

}

TY - JOUR

T1 - Glial inflammation and neurodegeneration induced by candoxin, a novel neurotoxin from Bungarus candidus venom

T2 - Global gene expression analysis using microarray

AU - Pachiappan, A.

AU - Thwin, M. M.

AU - Manikandan, J.

AU - Gopalakrishnakone, P.

PY - 2005/12/15

Y1 - 2005/12/15

N2 - Candoxin (PDB #1JGK), a three-finger neurotoxin from Bungarus candidus venom, inhibits post-synaptic neuromuscular and neuronal α7nACh-receptors, and induces delayed cell-death throughout the glial population. When applied to cultured human glial cell lines, candoxin (CDX) induced cell death in a concentration (EC50∼1 μM) and time dependent manner. Results of TUNEL-histochemistry further confirm CDX-induced brain (hippocampus, frontal cortex, and temporal regions) damage when administered intracerebroventricularly (i.c.v) in adult mice. In this study, we explored differential gene expression profiles following exposure of human glial (Hs 683) cell lines to CDX at various time intervals using Affymetrix-GeneChips. By means of MAS and GeneSpring analyses, 105 genes whose expression was significantly (P<0.01) altered by at least 3-fold were selected. Results of the genome analysis reveal that the potential role of CDX at molecular level involves the regulation of genes in signal transduction, ubiquitin-inflammation, mitochondrial-dysfunction, and damage-response pathways. In addition, using QRT-PCR and rationally designed specific CDX-binding peptide (P-NT.II), we identified the genes - IL7R, IL13RA2, IL-1β, TNFRSF12A, GADD45A, CD44 and IFI44 - that might play an important role in CDX-induced glial inflammation, DNA-damage and degeneration. These findings reveal new insight into the molecular mechanisms of glial-driven neurodegeneration after exposure to neurotoxins.

AB - Candoxin (PDB #1JGK), a three-finger neurotoxin from Bungarus candidus venom, inhibits post-synaptic neuromuscular and neuronal α7nACh-receptors, and induces delayed cell-death throughout the glial population. When applied to cultured human glial cell lines, candoxin (CDX) induced cell death in a concentration (EC50∼1 μM) and time dependent manner. Results of TUNEL-histochemistry further confirm CDX-induced brain (hippocampus, frontal cortex, and temporal regions) damage when administered intracerebroventricularly (i.c.v) in adult mice. In this study, we explored differential gene expression profiles following exposure of human glial (Hs 683) cell lines to CDX at various time intervals using Affymetrix-GeneChips. By means of MAS and GeneSpring analyses, 105 genes whose expression was significantly (P<0.01) altered by at least 3-fold were selected. Results of the genome analysis reveal that the potential role of CDX at molecular level involves the regulation of genes in signal transduction, ubiquitin-inflammation, mitochondrial-dysfunction, and damage-response pathways. In addition, using QRT-PCR and rationally designed specific CDX-binding peptide (P-NT.II), we identified the genes - IL7R, IL13RA2, IL-1β, TNFRSF12A, GADD45A, CD44 and IFI44 - that might play an important role in CDX-induced glial inflammation, DNA-damage and degeneration. These findings reveal new insight into the molecular mechanisms of glial-driven neurodegeneration after exposure to neurotoxins.

KW - Glial-degeneration and real-time PCR

KW - Inflammation

KW - Microarray

KW - TUNEL-assay

KW - Three-finger toxins

UR - http://www.scopus.com/inward/record.url?scp=28444464017&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=28444464017&partnerID=8YFLogxK

U2 - 10.1016/j.toxicon.2005.08.017

DO - 10.1016/j.toxicon.2005.08.017

M3 - Article

C2 - 16309724

AN - SCOPUS:28444464017

VL - 46

SP - 883

EP - 899

JO - Toxicon

JF - Toxicon

SN - 0041-0101

IS - 8

ER -