title: 3-Thiomethyl-5,6-(dimethoxyphenyl)-1,2,4-triazine improves neurite outgrowth and modulates MAPK phosphorylation and HSPs expression in H2O2-exposed PC12 cells.
abstract: Neurite outgrowth is an important aspect of neuronal plasticity and regeneration after neuronal injury. In this study we aimed to investigate the possible effect of 3-thiomethyl-5,6-dimethoxyphenyl-1,2,4-triazine (TDMT) on H(2)O(2)-induced impairment of neurite outgrowth. We found that TDMT could improve neurite outgrowth and neurite complexity in H(2)O(2)-exposed PC12 cells. Moreover, we found elevated levels of Hsp-70 and suppressed level of Hsp-90 in TDMT-treated cells in the presence of H(2)O(2). As another important signaling pathways that play role in neuritogenesis, as well as apoptosis, we measured the level of phosphorylated and total MAPKs proteins, JNK, ERK and p38 MAPK. We found that TDMT inhibits oxidative stress-induced phosphorylation of MAPKs. Since HSPs and MAPKs are both involved in coping with environmental changes, it will not be surprising if they can modify or augment each other's activity. Neuroprotective effect of this compound could represent a promising approach for treatment of neurodegenerative diseases.
authors.affiliation: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. khodagholi@sbmu.ac.ir
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.forename: Solaleh Khoramian
authors.initials: SK
authors.lastname: Tusi
authors.forename: Shabnam Zeighamy
authors.initials: SZ
authors.lastname: Alamdary
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.forename: Niloufar
authors.initials: N
authors.lastname: Ansari
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D014227:Triazines / Q000494:pharmacology*
chemical_list: C577054:3-thiomethyl-5,6-(dimethoxyphenyl)-1,2,4-triazine; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D018696:Neuroprotective Agents; D014227:Triazines; D020932:Nerve Growth Factor; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases