Disease relevance of Cnn1

• Structural fragility of blood vessels and peritoneum in calponin h1-deficient mice, resulting in an increase in hematogenous metastasis and peritoneal dissemination of malignant tumor cells [1].
• In the CN(-/-) mice receiving i.v. inoculations of B16 melanoma cells, significantly more metastatic nodules were formed in the lung than in the CN(+/+) mice [1].
• When B16 melanoma cells were injected i.p., the severity of peritonitis carcinomatosa was greater in CN(-/-) than in CN(+/+) mice [1].
• In recent studies, CNh1 was noted to suppress cell proliferation and tumorigenicity in leiomyosarcoma and tumor growth in fibrosarcoma cell lines [2].
• CONCLUSIONS: Calponin h1 may function as a tumor suppressor in leiomyosarcoma [3].

Psychiatry related information on Cnn1

• In the present study, we examined the effect of h1 calponin depletion on the metabolism and behavior of mice and found that the mutated mice showed increased locomotor activity, as well as increased intake of food and water, associated with the decreased number of neurons in the paraventricular nucleus of the hypothalamus (PVN) [4].

High impact information on Cnn1

• BACKGROUND: Calponin h1, a basic actin-binding protein capable of inhibiting smooth muscle contraction, is a constitutive element of smooth muscle cells [3].
• In this study, we sought to assess the effects (in vitro and in vivo) of increasing calponin h1 expression in leiomyosarcoma cells [3].
• Clinically, transfer of a calponin h1 complementary DNA into poorly differentiated leiomyosarcoma cells may be of potential therapeutic value through induction of a normal, differentiated cellular phenotype [3].
• However, in leiomyosarcoma (a type of smooth muscle neoplasm of the uterus), reduced expression of calponin h1 is observed, as we have reported previously [3].
• Southern blotting, reverse transcription-polymerase chain reaction analysis, western blotting, and immunohistochemistry were used to confirm DNA transfer and expression of the calponin h1 protein in neomycin-resistant clones [3].

Biological context of Cnn1

• As such, Cnn1 represents an ideal locus from which to dissect out regulatory elements that control its expression and hence the mature SMC phenotype [5].
• The down-regulation of Cnn1 mRNA during BC3H1 differentiation coincides with the induction of myogenin, a skeletal muscle transcription factor that is not present in SMC lineages [5].
• Transient transfection assays in cultured SMC demonstrated that high level SMC calponin promoter activity required no more than 549 nucleotides of 5 sequence [6].
• Expression of the smooth muscle cell calponin gene marks the early cardiac and smooth muscle cell lineages during mouse embryogenesis [6].
• Calponin-h1 is encoded by a 10.7-kilobase single copy gene composed of seven exons, which is part of a multigene family [7].

Anatomical context of Cnn1

• In this report, we describe a unique pattern of Cnn1 expression during the growth and differentiation of BC3H1 cells, a mouse cell line that has transcriptional characteristics of both smooth and skeletal muscle lineages [5].
• These results are the first to show reversible expression of Cnn1 and demonstrate the utility of the BC3H1 muscle cell line as a model system for the further characterization of Cnn1 gene regulation [5].
• Among three isoforms of calponin, h2-calponin is found in both smooth muscle and non-muscle cells [8].
• In particular, we frequently observed bleeding into the surrounding tissue from blood vessels of the ocular fundus in CN(-/-) mice [1].
• We have observed weak expression of calponin h1, which stabilizes the actin filament system, in blood vessels within human malignant tumors [1].

Associations of Cnn1 with chemical compounds

• Results from cycloheximide and actinomycin D studies suggest the existence of a labile repressor protein(s) that destabilizes the pool of Cnn1 mRNA and/or silences transcription of the Cnn1 locus [5].
• When fluorescein was injected i.v. into mice, the CN(-/-) mice exhibited a greater and more rapid leakage of fluorescein from the blood vessels of the ocular fundus compared with the CN(+/+) mice [1].
• Notably, expression of GFP h1 CaP, but not GFP h2 CaP, conferred increased resistance of the actin cytoskeleton to the actin polymerization antagonists cytochalasin B and latrunculin B, as well as to the protein kinase inhibitors H7-dihydrochloride and rho-kinase inhibitor Y-27632 [9].
• Expressing functional domains of mouse calponin: involvement of the region around alanine 145 in the actomyosin ATPase inhibitory activity of calponin [10].
• On the other hand, calponin bound strongly to nonfilamentous desmin tetramers and was incorporated into intermediate filaments when the two proteins were mixed in a buffer containing 6 M urea and dialyzed into a buffer containing 0.15 M NaCl [11].

Regulatory relationships of Cnn1

• To investigate a hypothesis that h2-calponin regulates the function of the actin cytoskeleton during cytokinesis, a smooth muscle-originated cell line (SM3) lacking calponin was transfected to express either sense or antisense h2-calponin cDNA and the effects on the rates of cell proliferation were examined [12].
• Calponin h1 suppresses tumor growth of Src-induced transformed 3Y1 cells in association with a decrease in angiogenesis [2].

Other interactions of Cnn1

• In contrast, the mRNA levels for calponin, expressed in the late stage of VSMC differentiation, were significantly higher in the wild-type mouse aorta as compared with the AT2 receptor-null mice, which correlates with expression of the AT2 receptor [13].
• We therefore generated calponin h1-deficient (CN(-/-)) mice to examine the effect of calponin h1 on the integrity of the barrier system in blood vessels against cancer metastasis [1].
• Calponin h1 (CNh1) is a basic actin-binding protein that is abundantly expressed in smooth muscle cells and involved in smooth muscle contraction by inhibiting actomyosin MgATPase [2].
• The localizations of calponin and caldesmon, and the correlation of their localizations with that of the actin cytoskeleton were analyzed by immunofluorescence microscopy using appropriate antibodies and rhodamine-phalloidin [14].
• The calponin family of F-actin-, tropomyosin- and calmodulin-binding proteins currently comprises three genetic variants [9].

Analytical, diagnostic and therapeutic context of Cnn1

• We have now investigated the effects of calponin (CaP) isoforms and their C-terminal deletion mutants on the actin cytoskeleton by time lapse video microscopy of GFP fusion proteins in living smooth muscle cells and fibroblasts [9].
• The purpose of this study is to evaluate the efficacy of i.p. CNh1 gene therapy against peritoneal dissemination of ovarian cancer [15].
• The expression of the contractile proteins, alpha-actin, smooth muscle myosin heavy chain-1 (SM1) and calponin present in smooth muscle cells (SMC) in the presence of oxidized low density lipoproteins (oxLDL) was investigated in two different cell cultures: the mouse smooth muscle cell line SVSC and rat smooth muscle cells (RSMC) [16].

References