Tbx20 promotes H9c2 cell survival against oxidative stress and hypoxia in vitro

Sustained and cardiac injury specific overexpression of Tbx20 provide cardiac protection of adult heart by preserving cardiac function increasing its survival rate post myocardial infarction (MI). However, the molecular mechanism underlying this protective pathway is largely unknown. Thus, in the current study, we examined Tbx20 and associated protective signaling pathway against two specific injury inductions. Injury inductions were done by imparting the cultured cardiac H9c2 cells with oxidative stress and hypoxia. Both stresses resulted in increased Tbx20 expression which activated the level of Nmyc1 and Bmp2 showing increased cellular proliferative rate. However, it was not sufficient to overcome the stress responses owing to increased apoptosis. The sustained overexpression of Tbx20, prior to injury induction, showed further enhancement in the expression patterns of Nmyc1 and Bmp2 that accelerated the proliferation rate, thus promoting the formation of increased number of viable cells, reducing the cellular apoptosis post injury. Moreover, overexpressed Tbx20 inhibits cellular hypertrophy post injury by increasing the activation level of Yap1 and together may follow a feedback loop mechanism downregulating the p-Akt activity. Therefore, Tbx20 overexpression has been found to be sufficient to impart cardiac protection post injury by triggering its associated signaling molecules.

Comparative QSAR modeling of COX-2 inhibitor 1,2-diarylimidazoles using E-state and physicochemical parameters.

Considering importance of developing selective COX-2 inhibitors, COX-2 binding affinity data of 4-(2-aryl-1-imidazolyl)-phenyl methyl sulfones and sulfonamides (n = 83) have been modeled using electrotopological state (E-state) index as electronic parameter, hydrophobic substituent constant (pi) and molar refractivity (MR) of aryl ring substituents as lipophilic and steric parameters, respectively. Additionally, suitable dummy parameters have been used for the development of multiple regression equations in a stepwise manner. The study suggests that lipophilicity of ortho, meta and para substituents of the aryl ring increases the binding affinity, while molar refractivity (MR) of ortho and meta substituents of the aryl ring decreases the binding affinity. Again, electron-withdrawing substituents at meta and para positions of the aryl ring increase the binding affinity. Additionally, a 4-fluoro substituent on the aryl ring, a trifluoromethyl substituent at R position and simultaneous presence of 3-chloro and 4-methyl groups on the aryl ring are conducive to the binding affinity. Also, an amino substituent is preferred over a methyl group at R2 position suggesting preference of the sulfonamide moiety over the methyl sulfone moiety for the COX-2 binding affinity. Furthermore, importance of E-state values of different atoms in the generated relations suggests the influence of electron density distribution over the 1,2-diarylimidazole nucleus for the binding affinity. For this data set, E-state parameters perform better as electronic parameters in comparison to Hammett sigma parameters. When lipophilic whole molecular descriptor (ClogP) is used, instead of hydrophobic substituent constant (pi), the former performs better than the latter.