Ca2+ Modulation System of Myometrial Contraction During Gestation
Robert E. Garfield, Thomas N. Tabb in Control of Uterine Contractility, 2019
Phorbol ester increases sensitization of the contractile apparatus without change of [Ca2+]i in rabbit mesenteric artery, porcine coronary artery, or pregnant rat myometrium.34,35,72 Activation of protein kinase C by stimulation with phorbol ester has been reported to result in MLC phosphorylation at sites other than serine-19.4,6 It has been also reported that contractions elicited by agonists that trigger phosphoinositide turnover do not involve PKC-catalyzed phosphorylation of either myosin or MLCK.4 Recently, it has been demonstrated that the putative thin-filament regulatory proteins, calponin and caldesmon, may be involved in the agonist-induced increase in myofilament Ca2+ sensitivity. Unphosphorylated calponin and caldesmon bind to actin and depress actin-activated myosin ATPase activity.62,81 In rabbit myometrium caldesmon inhibits myosin ATPase activity.55 Translocation of PKC to the sarcolemma activated by agonist is considered to result in phosphorylation of caldesmon and calponin to produce slow sustained contractions.4,62,81 Thus, increased protein kinase C activity may therefore relieve the inhibitory effects of calponin or caldesmon and account for phorbol ester-induced increase in force shown in our study.
The Calcium-Calmodulin System
Enrique Pimentel in Handbook of Growth Factors, 2017
Calcium binds to complexes of calmodulin and several classes of calmodulin-binding proteins,196 and a prominent member of such proteins is caldesmon,197,198 a calmodulin-binding and F-actin-binding protein that is involved in the mechanism by which the Ca2+-dependent regulatory action of calmodulin is transmitted to F-actin filaments.199,200 Caldesmon was first isolated from smooth muscle of chicken gizzard as a 155-kDa protein that binds to actin-tropomyosin filaments, but the molecular weight of monomeric caldesmon in solution is 93 kDa.201 The actin cross-linking, bundling, and polymerizing properties of caldesmon in vitro suggest that its function may be related to cytoskeletal structures in vivo. Direct interaction between tropomyosin and caldesmon may contribute to regulate smooth muscle contraction upon binding of Ca2+ to the actin-bound calsdesmon.202 Caldesmon is present in a diversity of cells. Two forms of caldesmon (molecular weight in the range of 120 to 150 and 70 to 80 kDa, respectively) have been detected in a wide variety of smooth muscle and nonmuscle cells. The high molecular weight form of caldesmon is more specific for smooth muscle, whereas the low molecular weight form is widely distributed in tissues and cells with the exception of smooth muscle.203 Caldesmon may play a major role in the regulation of smooth muscle and nonmuscle contractile events, which implicates its involvement in a wide variety of biological phenomena including contraction, cell movement, cell shape change, and endocytosis. Caldesmon is found in bovine aorta and uterus, in adrenal medulla, and in human platelets as well as in cultured fibroblasts, where it is present as a 77-kDa protein and is localized in the cellular stress fibers and leading edges in close association with actin filaments. In nonmuscle cells, the calmodulin-caldesmon system may play a regulatory role in cellular functions associated with actin-containing microfilaments, such as cellular morphology and locomotion, membrane ruffling, and cell adhesion to a substratum. Caldesmon is present in intact platelets and may be phosphorylated by protein kinase C.204,205 The possible physiological significance of caldesmon phosphorylation is still uncertain but nonmuscle caldesmon is phosphorylated by the cdc2 kinase during mitosis, which reduces its binding affinity for both actin and calmodulin, suggesting that cdc2 may cause microfilament reorganization during mitosis.206,207 RSV-transformed cells may contain decreased caldesmon concentrations, and the intracellular distribution of caldesmon in these cells is changed to a diffuse and blurred appearance.200 These alterations may be important in relation to the morphological and functional expression of a transformed phenotype.
A rare case of orbital angioleiomyoma
Published in Orbit, 2021
Shiao Wei Wong, James Laybourne, Luciane Irion, Anne Cook
Histopathology is key for diagnosis. Henderson and Harrison4 and Wolter2 reported the earliest cases of angioleiomyoma which predates the Morimoto1 classifications. However more recent reports have described the morphological features of the orbital angioleiomyomas excised. The cavernous type was the most commonly reported (which includes our case), followed by the venous type and then the solid type (Table 1). On immunohistochemistry the lesion shows positivity for alpha smooth muscle actin (Figure 5), vimentin, desmin, calponin and h-caldesmon. CD31 and CD34 highlight the endothelial component (Figure 4a,4b). Angioleiomyoma lacks expression for HMB45 and oestrogen receptors. Histopathology and immunohistochemistry therefore help to differentiate angioleiomyoma from closely related lesions such as leiomyoma, angiomyoma, angiomyofibroma and angiomyolipoma.9,13,13
Difference in immunohistochemical characteristics between Takayasu arteritis and giant cell arteritis: It may be better to distinguish them in the same age
Published in Modern Rheumatology, 2019
Atsushi Kurata, Akira Saito, Hirotsugu Hashimoto, Koji Fujita, Shin-ichiro Ohno, Hiroshi Kamma, Toshitaka Nagao, Shigeto Kobayashi, Akira Yamashina, Masahiko Kuroda
In the present study, we assessed TAK and GCA specimens mainly through use of immunohistochemistry, with a view to elucidation of similarities or differences between these two disorders. To the best of our knowledge, such immunohistochemical comparisons have not been performed to date, except for one study which compared necrotizing aortitis in patients younger than 65 years suggestive of TAK with non-necrotizing aortitis suggestive of GCA [10]. However, in that study, grouping did not conform to clinical criteria, cases suggestive of TAK exhibited no sex predominance, and inflammatory cells were assessed only in the media and adventitia. In the present study we compared cases of clinically diagnosed TAK with GCA and compared three layers including intima. Furthermore, we used antibodies against h-Caldesmon for smooth muscle cells, CD79a for B-cells, CD138 for plasma cells, and fascin for dendritic cells for the first time. Several novel features were found in TAK compared with GCA, including greater adventitial lymphoplasmacytic infiltration and smaller numbers of intimal dendritic cells along with overall more B-cells, more CD8+ cells, and a lower CD4/8 ratio.
Metastatic TFE3-overexpressing renal clear cell carcinoma with dense granules: a histological, immunohistochemical, and ultrastructural study
Published in Ultrastructural Pathology, 2018
Shoujun Chen, Elba A. Turbat-Herrera, Guillermo A. Herrera, Meghna Chadha, Rodney E. Shackelford, Eric X. Wei
Special stains and IHS studies were performed on paraffin sections of pleural biopsies. The tumor cells were positive for Periodic acid–Schiff stain, but negative for Periodic acid–Schiff-diastase (PAS-D) stain. The neoplastic cells were positive for caldesmon (subset of cellular elements), CD10 (small subset and equivocal), cyclin D1, smooth muscle actin (partial), p53, and vimentin (diffuse strong), and negative for AE1/AE3, CAM5.2, alpha 1 antitrypsin, calretinin, CD31, CD34, CD45, CD68, CD99, CD117, CD163, CK7, CK20, desmin, HMB45, MART-1, muscle-specific actin, myogenin, PAX-8, PLAP, RCC, S-100, and WT-1. Ki-67 showed tumor proliferation index at about 20–40%. Subsequently, TFE3 immunostain was performed to explore the possibility of RCC XP11.2 subtype. IHC for TFE3 protein was overexpressed as compared to the positive and negative controls (Figure 3). However, no rearrangement of TFE3 gene was identified by the XP11.2 break-apart FISH studies.
Related Knowledge Centers
- Calponin
- Immunochemistry
- Protein
- Smooth Muscle
- Gene
- Calmodulin-Binding Proteins