Endoplasmic Reticulum Stress-Related Inflammation and Cardiovascular Diseases

The endoplasmic reticulum (ER) is the site of synthesis and maturation of proteins designed for secretion or for localization on the cell membrane. Various types of stress from both inside and outside cells disturb ER function, thus causing unfolded or misfolded proteins to accumulate in the ER. To improve and maintain the ER functions against such stresses, the ER stress response pathway is activated. However, when the stress is prolonged or severe, apoptosis pathways are activated to remove damaged cells. It was recently reported that the ER stress pathway is also involved in the inflammatory response, whereby inflammation induces ER stress, and ER stress induces an inflammatory response. Therefore, the ER stress response pathway is involved in various diseases, including cardiovascular diseases such as atherosclerosis and ischemic diseases, in various ways. The ER stress pathway may represent a novel target for the treatment of these diseases

Upregulation of ANGPTL6 in mouse keratinocytes enhances susceptibility to psoriasis

Psoriasis is a chronic inflammatory skin disease marked by aberrant tissue repair. Mutant mice modeling psoriasis skin characteristics have provided useful information relevant to molecular mechanisms and could serve to evaluate therapeutic strategies. Here, we found that epidermal ANGPTL6 expression was markedly induced during tissue repair in mice. Analysis of mice overexpressing ANGPTL6 in keratinocytes (K14-Angptl6 Tg mice) revealed that epidermal ANGPTL6 activity promotes aberrant epidermal barrier function due to hyperproliferation of prematurely differentiated keratinocytes. Moreover, skin tissues of K14-Angptl6 Tg mice showed aberrantly activated skin tissue inflammation seen in psoriasis. Levels of the proteins S100A9, recently proposed as therapeutic targets for psoriasis, also increased in skin tissue of K14-Angptl6 Tg mice, but psoriasis-like inflammatory phenotypes in those mice were not rescued by S100A9 deletion. This finding suggests that decreasing S100A9 levels may not ameliorate all cases of psoriasis and that diverse mechanisms underlie the condition. Finally, we observed enhanced levels of epidermal ANGPTL6 in tissue specimens from some psoriasis patients. We conclude that the K14-Angptl6 Tg mouse is useful to investigate psoriasis pathogenesis and for preclinical testing of new therapeutics. Our study also suggests that ANGPTL6 activation in keratinocytes enhances psoriasis susceptibility

LASER INDUCED FLUORESCENCE SPECTROSCOPY OF THE SiNSi RADICAL II: IDENTIFICATIONS OF THE A~2A1,B~2B1\widetilde A^2A_1, \widetilde B^2B_1, AND D~2Σg+\widetilde D^2\Sigma_g^+ STATES

Author Institution: Department of Basic Science, The University of Tokyo, Tokyo 153-8902, Japan; Faculty of Information Sciences, Hiroshima City University, Hiroshima 731-3194, JapanAmong the LIF spectra of SiNSi observed in the near UV region, another band system with fluorescence lifetimes of 30 ns was identified. From detailed analyses of the rotational structures of the observed vibronic bands, they were assiged to the $\widetilde D^2\Sigma_g^+ - X^2\Pi_g$ band system of SiNSi, which is a symmetry forbidden transition borrowing intensity from vibronic mixings. Dispersed fluorescence spectra from SVL levels of the $\widetilde D$ state show distinct features around 13,000 cm$^{-1}$ above the ground vibronic state, which were assigned to transitions to two electronic states $\widetilde A^2A_1$ and $\widetilde B^2B_1$, correlated to a $^2\Pi_u$ state at the limit of linearity. LIF spectra were observed in the corresponding region from 13,000 to 14,000 cm$^{-1}$ to confirm the assignment. Dispersed fluorescence spectra from the visible transitions gave vibrational term energies for high lying bending vibrational levels in the ground state, showing that they are bent$-$linear transitions

LASER INDUCED FLUORESCENCE SPECTROSCOPY OF THE SiNSi RADICAL I:\\THE C~\tilde{C} 2Δu^2\Delta_u -- X~\tilde{X} 2Πg^2\Pi_g TRANSITION

Author Institution: Faculty of Information Sciences; Hiroshima City University; Hiroshima 731-3194, Japan; Department of Basic Science; The University of Tokyo; Meguro 153-8902, JapanWe have generated SiNSi in a supersonic free jet expansion, and measured the laser induced fluorescence (~LIF~) spectrum in the ultraviolet (~UV~) region. Dispersed fluorescence (~DF~) spectra from the single vibronic levels (~SVL~) have also been recorded by exciting each observed vibronic band. On the basis of the rotational analyses of the observed vibronic bands and the appearance the vibrational structure in the DF spectra, several bands were attributed to the $\tilde{C}$ $^2\Delta_u$ -- $\tilde{X}$ $^2\Pi_g$ system of SiNSi. From the analysis of the $0_0^0$ band with an origin of 29,261.61 cm$^{-1}$, the effective spin-orbit constants were determined to be 140.59 and 2.623 cm$^{-1}$ for the $\tilde{X}$ $^2\Pi_g$ and $\tilde{C}$ $^2\Delta_u$ states, respectively. In total, ten vibronic levels including the zero vibrational level were assigned to the $\tilde{C}$ $^2\Delta_u$ state, and the vibonic structure was analyzed considering the Renner-Teller interaction