Endothelial Shc Regulates Arteriogenesis Through Dual Control of Arterial Specification and Inflammation via the Notch and Nuclear Factor- -Light-Chain-Enhancer of Activated B-Cell Pathways

Arteriogenesis, the shear stress-driven remodeling of collateral arteries, is critical in restoring blood flow to ischemic tissue following a vascular occlusion. Our previous work has shown that the adaptor protein Shc mediates endothelial responses to shear stress in vitro

Two-Photon Activation of <i>p</i>‑Hydroxyphenacyl Phototriggers: Toward Spatially Controlled Release of Diethyl Phosphate and ATP

Two-photon activation of the <i>p</i>-hydroxyphenacyl (<i>p</i>HP) photoactivated protecting group is demonstrated for the first time using visible light at 550 nm from a pulsed laser. Broadband two-photon absorption measurements reveal a strong two-photon transition (>10 GM) near 4.5 eV that closely resembles the lowest-energy band at the same total excitation energy in the one-photon absorption spectrum of the <i>p</i>HP chromophore. The polarization dependence of the two-photon absorption band is consistent with excitation to the same S₃ (¹ππ*) excited state for both one- and two-photon activation. Monitoring the progress of the uncaging reaction under nonresonant excitation at 550 nm confirms a quadratic intensity dependence and that two-photon activation of the uncaging reaction is possible using visible light in the range 500–620 nm. Deprotonation of the <i>p</i>HP chromophore under mildly basic conditions shifts the absorption band to lower energy (3.8 eV) in both the one- and two-photon absorption spectra, suggesting that two-photon activation of the <i>p</i>HP chromophore may be possible using light in the range 550–720 nm. The results of these measurements open the possibility of spatially and temporally selective release of biologically active compounds from the <i>p</i>HP protecting group using visible light from a pulsed laser

Calcium Channel TRPV6 Is Involved in Murine Maternal–Fetal Calcium Transport

Maternal–fetal calcium (Ca2+) transport is crucial for fetal Ca2+ homeostasis and bone mineralization. In this study, the physiological significance of the transient receptor potential, vanilloid 6 (TRPV6) Ca2+ channel in maternal–fetal Ca2+ transport was investigated using Trpv6 knockout mice. The Ca2+ concentration in fetal blood and amniotic fluid was significantly lower in Trpv6 knockout fetuses than in wildtypes. The transport activity of radioactive Ca2+ (45Ca) from mother to fetuses was 40% lower in Trpv6 knockout fetuses than in wildtypes. The ash weight was also lower in Trpv6 knockout fetuses compared with wildtype fetuses. TRPV6 mRNA and protein were mainly localized in intraplacental yolk sac and the visceral layer of extraplacental yolk sac, which are thought to be the places for maternal–fetal Ca2+ transport in mice. These expression sites were co-localized with calbindin D9K in the yolk sac. In wildtype mice, placental TRPV6 mRNA increased 14-fold during the last 4 days of gestation, which coincides with fetal bone mineralization. These results provide the first in vivo evidence that TRPV6 is involved in maternal–fetal Ca2+ transport. We propose that TRPV6 functions as a Ca2+ entry pathway, which is critical for fetal Ca2+ homeostasis