Two-pore channel 2 is required for soluble adenylyl cyclase-dependent regulation of melanosomal pH and melanin synthesis.

Melanosomal pH is important for the synthesis of melanin as the rate-limiting enzyme, tyrosinase, is very pH-sensitive. The soluble adenylyl cyclase (sAC) signaling pathway was recently identified as a regulator of melanosomal pH in melanocytes; however, the melanosomal proteins critical for sAC-dependent regulation of melanosomal pH were undefined. We now systematically examine four well-characterized melanosomal membrane proteins to determine whether any of them are required for sAC-dependent regulation of melanosomal pH.

Distinct cAMP Signaling Microdomains Differentially Regulate Melanosomal pH and Pigmentation.

cAMP signaling is a well-established regulator of melanin synthesis. Two distinct cAMP signaling pathways-the transmembrane adenylyl cyclase pathway, activated primarily by the MC1R, and the soluble adenylyl cyclase (sAC) pathway-affect melanin synthesis. The sAC pathway affects melanin synthesis by regulating melanosomal pH, and the MC1R pathway affects melanin synthesis by regulating gene expression and post-translational modifications.

Soluble adenylyl cyclase contributes to imiquimod-mediated inflammation and is a potential therapeutic target in psoriasis.

Cyclic AMP (cAMP) has a key role in psoriasis pathogenesis, as indicated by the therapeutic efficacy of phosphodiesterase inhibitors that prevent the degradation of cAMP. However, whether soluble adenylate cyclase (sAC) (encoded by the ADCY10 gene), which is an important source for cAMP, is involved in Th17 cell-mediated inflammation or could be an alternative therapeutic target in psoriasis is unknown. We have utilized the imiquimod model of murine psoriasiform dermatitis to address this question.

A nuclear cAMP microdomain suppresses tumor growth by Hippo pathway inactivation.

Cyclic AMP (cAMP) signaling is localized to multiple spatially distinct microdomains, but the role of cAMP microdomains in cancer cell biology is poorly understood. Here, we present a tunable genetic system that allows us to activate cAMP signaling in specific microdomains. We uncover a nuclear cAMP microdomain that activates a tumor-suppressive pathway in a broad range of cancers by inhibiting YAP, a key effector protein of the Hippo pathway, inside the nucleus.

Flow cytometric characterization of the hemocytes of blood cockles Anadara broughtonii (Schrenck, 1867), Anadara kagoshimensis (Lischke, 1869), and Tegillarca granosa (Linnaeus, 1758) as a biomarker for coastal environmental monitoring.

Marine bivalves are often used as a sentinel species in coastal environmental monitoring since changes in the environmental quality are often well preserved in their cells and tissues. Anadara and Tegillarca species of Arcidae, the blood cockles, are considered to be good sentinel species in monitoring coastal pollution and ecosystem health because they are distributed widely in the subsurface of intertidal mudflats. Internal cellular defense of the blood cockles to physical and biological stresses is mediated by the circulating hemocytes, while their hemocyte types and functions are poorly studied.

Biological Effects of the Herbal Plant-Derived Phytoestrogen Bavachin in Primary Rat Chondrocytes.

The aim of this study was to examine the anabolic and anticatabolic functions of bavachin in primary rat chondrocytes. With bavachin treatment, chondrocytes survived for 21 d without cell proliferation, and the proteoglycan content and extracellular matrix increased. Short-term monolayer culture of chondrocytes showed that gene induction of both aggrecan and collagen type II, major extracellular matrix components, was significantly upregulated by bavachin.

Development of an Experimental Animal Model for Lower Back Pain by Percutaneous Injury-Induced Lumbar Facet Joint Osteoarthritis.

We report generation and characterization of pain-related behavior in a minimally invasive facet joint degeneration (FJD) animal model in rats. FJD was produced by a non-open percutaneous puncture-induced injury on the right lumbar FJs at three consecutive levels. Pressure hyperalgesia in the lower back was assessed by measuring the vocalization response to pressure from a force transducer.

Radiologic evaluation of degeneration in isthmic and degenerative spondylolisthesis.

Study Design: A cross-sectional imaging study.

Purpose: The objective was to assess the degree of degeneration and the associated factors through imaging studies of the lesion segment and the adjacent superior and inferior segments of isthmic and degenerative spondylolisthesis.

Overview Of Literature: Few articles existed for degeneration and related factors in isthmic and degenerative spondylolisthesis.