Cardiovascular response to small-molecule APJ activation

A small molecule transcriptional activation domain.

Artificial transcriptional activators are excellent tools for studying the mechanistic details of transcriptional regulation. Furthermore, as the correlation between a wide range of human diseases and misregulated transcription becomes increasingly evident, such molecules may in the long run serve as the basis for transcription-based therapeutic agents. The greatest challenge in this arena has ...

Apelin-APJ signaling is a critical regulator of endothelial MEF2 activation in cardiovascular development.

RATIONALE The peptide ligand apelin and its receptor APJ constitute a signaling pathway with numerous effects on the cardiovascular system, including cardiovascular development in model organisms such as xenopus and zebrafish. OBJECTIVE This study aimed to characterize the embryonic lethal phenotype of the Apj-/- mice and to define the involved downstream signaling targets. METHODS AND RESU...

Small molecule modulators of antioxidant response pathway.

Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor that regulates Antioxidant Response Element (ARE)-mediated transcription of a plethora of antioxidant and protective genes to counteract the harmful effects of reactive oxygen species or environmental carcinogens. Studies have demonstrated that pre-emptive activation of the Nrf2-ARE pathway reinforces the cellular defense mecha...

Endoplasmic reticulum stress-independent activation of unfolded protein response kinases by a small molecule ATP-mimic

Two ER membrane-resident transmembrane kinases, IRE1 and PERK, function as stress sensors in the unfolded protein response. IRE1 also has an endoribonuclease activity, which initiates a non-conventional mRNA splicing reaction, while PERK phosphorylates eIF2α. We engineered a potent small molecule, IPA, that binds to IRE1's ATP-binding pocket and predisposes the kinase domain to oligomerization,...

A novel APJ signaling cascade that regulates cardiovascular development.