title: JNK1 and JNK3 play a significant role in both neuronal apoptosis and necrosis. Evaluation based on in vitro approach using tert-butylhydroperoxide induced oxidative stress in neuro-2A cells and perturbation through 3-aminobenzamide.
abstract: In spinal cord injury (SCI), oxidative stress in the penumbra of the injury site is a characteristic feature. The predominance of necrosis over apoptosis in the ensuing delayed cell death results in progressive waves of necrosis affecting neighboring cells and thus exaggerates the severity of the lesion. Necrosis has been classified into subtypes based on the active molecular players and parthanatos is one among them, which is characterized by the over activation of PARP1 as the pre-mitochondrial event that triggers necrosis. Parthanatos being the necrosis mode reported in SCI, we intended to study the molecular players in the elusive pre-mitochondrial events of PARP1 over activation using an in vitro model. tert-Butylhydroperoxide (tBuOOH) was reported to induce oxidative stress in various cell types including Neuro-2A cells. Using a tailored protocol, a predominantly PARP1 mediated necrotic mode of cell death was obtained in Neuro-2A cells using tBuOOH. By perturbing the progress of necrosis using 3-amniobenzamide, a known PARP1 inhibitor, it was found that JNK1 and JNK3 but not JNK2 were involved in pre-mitochondrial stages of PARP1 mediated cell death. Given that JNK1 and JNK3 play a role in apoptosis also, they may serve as common targets to counter both apoptosis and necrosis. The in vitro model used in the present study may be useful in delineating molecular mechanisms in necrosis.
authors.affiliation: Department of Anatomy, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamilnadu, India.
authors.forename: Vijaya Prakash Krishnan
authors.initials: VPK
authors.lastname: Muthaiah
authors.affiliation: Department of Anatomy, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamilnadu, India.
authors.forename: Felicia Mary
authors.initials: FM
authors.lastname: Michael
authors.affiliation: Department of Anatomy, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamilnadu, India.
authors.forename: Tamilselvi
authors.initials: T
authors.lastname: Palaniappan
authors.affiliation: Department of Anatomy, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamilnadu, India.
authors.forename: Sridhar Skylab
authors.initials: SS
authors.lastname: Rajan
authors.affiliation: Department of Anatomy, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamilnadu, India.
authors.forename: Kirubhanand
authors.initials: K
authors.lastname: Chandrasekar
authors.affiliation: Department of Anatomy, Dr. ALM Post Graduate Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai 600113, Tamilnadu, India. Electronic address: sankar@unom.ac.in.
authors.forename: Sankar
authors.initials: S
authors.lastname: Venkatachalam
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001549:Benzamides / Q000633:toxicity*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation; D005786:Gene Expression Regulation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D048057:Mitogen-Activated Protein Kinase 10 / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D009336:Necrosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D020122:tert-Butylhydroperoxide / Q000633:toxicity*
chemical_list: D001549:Benzamides; D019253:Proto-Oncogene Proteins c-bcl-2; C025160:3-aminobenzamide; D020122:tert-Butylhydroperoxide; D048057:Mitogen-Activated Protein Kinase 10; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D053148:Caspase 3
keywords: 3-Aminobenzamide; JNK role in neuronal death; Neuro-2A cells; Neuronal apoptosis; Neuronal necrosis; PARP1 overactivation