In vitro analysis revealed “that propranolol reduces the expression of HIF-1 alpha in hemangioma cells in a dose- and time-dependent manner, mainly by acting on P2-AR. Interestingly, it was observed that overexpression of HIF-1 alpha apparently abrogated the inhibitory effects GSI-IX nmr of propranolol on vascular endothelial growth factor (VEGF) expression and cell growth. Our data further demonstrated that propranolol inhibited the signal transducer and activator of transcription 3 (STAT3), a critical oncogenic signaling molecule,
and the anti-apoptotic protein Bcl-2. Additionally, overexpression of HIF-1 alpha significantly reversed the inhibitory effects of propranolol on STAT3 signaling. In a mouse xenograft hemangioma model, overexpression of HIF-1 alpha significantly attenuated the therapeutic effects of propranolol and inhibited propranolol-induced hemangioma cell apoptosis. Moreover, the protein levels of VEGF, phosphorylated STAT3, total STAT3 and Bcl-2 were significantly upregulated by HIF-1 alpha overexpression in propranolol-treated nude mice bearing hemangiomas. Collectively, our data provide evidence that propranolol may regress infantile hemangiomas by suppressing VEGF and STAT3 signaling pathways in an HIF-1 alpha-dependent manner.”
“The expanding repertoire of genetically encoded
biosensors constructed from variants of Aequorea victoria green fluorescent protein (GFP) enable the imaging of a variety LY3039478 in vitro of intracellular biochemical BTSA1 mouse processes. To facilitate the imaging
of multiple biosensors in a single cell, we undertook the development of a dimerization-dependent red fluorescent protein (ddRFP) that provides an alternative strategy for biosensor construction. An extensive process of rational engineering and directed protein evolution led to the discovery of a ddRFP with a K-d of 33 mu M and a 10-fold increase in fluorescence upon heterodimer formation. We demonstrate that the dimerization-dependent fluorescence of ddRFP can be used for detection of a protein-protein interaction in vitro, imaging of the reversible Ca2+-dependent association of calmodulin and M13 in live cells, and imaging of caspase-3 activity during apoptosis.”
“Expression of STAT-3/pSTAT3 in colorectal cancer (CRC) patients of Indian origin was studied to assess its significance in early detection and apoptosis regulation. Colorectal tissues with malignant lesions were STAT3/pSTAT3 positive in 66% of the cases and among these positive cases, well differentiated, moderately differentiated and poorly differentiated cancers were 86%, 60% and 0% respectively. All CRC specimens studied were immunoreactive with anti-carcinoembryonic antigen antibody.