Melanopsin (OPN4) is a novel player in skin homeostasis and attenuates UVA-induced effects.

The presence of melanopsin (OPN4) has been shown in cultured murine melanocytes and was associated with ultraviolet A radiation (UVA) reception. Here we demonstrated the protective role of OPN4 in skin physiology and the increased UVA-induced damage in its absence. Histological analysis showed a thicker dermis and thinner hypodermal white adipose tissue layer in Opn4-/- (KO) mice than in wild-type (WT) animals. Proteomics analyses revealed molecular signatures associated with proteolysis, remodeling chromatin, DNA damage response (DDR), immune response, and oxidative stress coupled with antioxidant responses in the skin of Opn4 KO mice compared to WT. Skin protein variants were found in Opn4 KO mice and Opn2, Opn3, and Opn5 gene expressions were increased in the genotype. We investigated each genotype response to UVA stimulus (100 kJ/m2). We found an increase of Opn4 gene expression following stimulus on the skin of WT mice suggesting melanopsin as a UVA sensor. Proteomics findings suggest that UVA decreases DDR pathways associated with ROS accumulation and lipid peroxidation in the skin of Opn4 KO mice. Relative changes in methylation (H3-K79) and acetylation sites of histone between genotypes and differentially modulated by UVA stimulus were also observed. We also identified alterations of molecular traits of the central hypothalamus-pituitary- adrenal (HPA) and the skin HPA-like axes in the absence of OPN4. Higher skin corticosterone levels were detected in UVA-stimulated Opn4 KO compared to irradiated WT mice. Taken altogether, functional proteomics associated with gene expression experiments allowed a high-throughput evaluation that suggests an important protective role of OPN4 in regulating skin physiology in the presence and absence of UVA radiation.

Lack of TRPV1 Channel Modulates Mouse Gene Expression and Liver Proteome with Glucose Metabolism Changes.

To investigate the role of the transient receptor potential channel vanilloid type 1 (TRPV1) in hepatic glucose metabolism, we analyzed genes related to the clock system and glucose/lipid metabolism and performed glycogen measurements at ZT8 and ZT20 in the liver of C57Bl/6J (WT) and Trpv1 KO mice. To identify molecular clues associated with metabolic changes, we performed proteomics analysis at ZT8. Liver from Trpv1 KO mice exhibited reduced Per1 expression and increased Pparα, Pparγ, Glut2, G6pc1 (G6pase), Pck1 (Pepck), Akt, and Gsk3b expression at ZT8. Liver from Trpv1 KO mice also showed reduced glycogen storage at ZT8 but not at ZT20 and significant proteomics changes consistent with enhanced glycogenolysis, as well as increased gluconeogenesis and inflammatory features. The network propagation approach evidenced that the TRPV1 channel is an intrinsic component of the glucagon signaling pathway, and its loss seems to be associated with increased gluconeogenesis through PKA signaling. In this sense, the differentially identified kinases and phosphatases in WT and Trpv1 KO liver proteomes show that the PP2A phosphatase complex and PKA may be major players in glycogenolysis in Trpv1 KO mice.

Calcium handling proteins: structure, function, and modulation by exercise.

Heart failure is a serious public health issue with a growing prevalence, and it is related with the aging of the population. Hypertension is identified as the main precursor of left ventricular hypertrophy and therefore can lead to diastolic dysfunction and heart failure. Scientific studies have confirmed the beneficial effects of the physical exercise by reducing the blood pressure and improving the functional status of the heart in hypertension. Several proteins are involved in the mobilization of calcium during the coupling excitation-contraction process in the heart among those are sarcoplasmic reticulum Ca(2+)-ATPase, phospholamban, calsequestrin, sodium-calcium exchanger, L-type calcium's channel, and ryanodine receptors. Our goal is to address the beneficial effects of exercise on the calcium handling proteins in a heart with hypertension.