Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.22.56 (caspase-3)
 35,750 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary biliary cirrhosis is characterized by the immune-mediated, progressive destruction of interlobular bile ducts. Lymphoid cells migrate into the biliary epithelial layer through integrin alpha(4)/fibronectin interaction and are responsible for chronic destructive cholangitis. The bile ducts express intercellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1), and infiltrating lymphocytes express LFA1 and VLA4, facilitating their interaction. Epithelioid granulomas contain foamy cells ingesting biliary lipids, and CD1d was detectable in epithelioid granulomas, suggesting that the biliary substance(s) which are leaked is a trigger for chronic destructive cholangitis. Apoptotic biliary destruction is brought about by antigen-specific and non-specific reactions. Shrunken biliary epithelial cells with pyknotic nuclei positive for terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelling (TUNEL) may reflect apoptotic processes. Increased expression of caspase-3 and -8 with DNA fragmentation factor on the bile ducts may reflect molecular events during apoptosis, and down-regulation of Bcl-2 of biliary epithelial cells seems to facilitate apoptosis. Multiple factors, particularly the Fas system, are stimuli of apoptosis. Anoikis with decreased biliary expression of integrin 6, a ligand for laminin, may also be involved in biliary epithelial apoptosis.
Baillieres Best Pract Res Clin Gastroenterol 2000 Aug
PMID:Destruction of bile ducts in primary biliary cirrhosis. 1097 14

Bestrophin 3 (Best-3) is expressed in a variety of tissues, such as cardiac, smooth muscle and renal tissues, and it is highly expressed in rat basilar arterial smooth muscle cells (BASMCs). Lee et al. (Biochim Biophys Acta 1823:1864-1876, 2012) reported that Best-3 prevented apoptotic cell death induced by endoplasmic reticulum stress. In the present study, we used small interference RNA (siRNA) and bestrophin 3 cDNA transfection strategy to investigate whether Best-3 can provide a protective effect on apoptosis induced by hydrogen peroxide (H2O2) in BASMCs and studied the underlying mechanisms. We found that silencing of Best-3 with siRNA resulted in an increased H2O2-induced apoptosis and a decreased cell viability, whereas overexpression of Best-3 significantly prevented the apoptotic cell death and increased the cell viability. Overexpression of Best-3 could stabilize the mitochondrial membrane potential, increase the ratio of Bcl-2/Bax, and decrease cytochrome c release and caspase-3 activation. In contrast, silencing of Best-3 produced the opposite effects. Our present data strongly suggest that Best-3 inhibits apoptosis induced by H2O2 in BASMCs through mitochondria dependent pathway.
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PMID:Mitochondria dependent pathway is involved in the protective effect of bestrophin-3 on hydrogen peroxide-induced apoptosis in basilar artery smooth muscle cells. 2346 20

Naringin, the primary active compound of the traditional Chinese medicine Rhizoma drynariae, possesses many pharmacological activities. The present study is an effort to explore the anti-osteoporosis potential of naringin in vivo and in vitro. In vivo, we used ovariectomized rats to clarify the mechanisms by which naringin anti-osteoporosis. In vitro, we used osteoclasts to investigate naringin promotes osteoclasts apoptosis. Naringin was effective at enhancing BMD, trabecular thickness, bone mineralization, and mechanical strength in a dose-dependent manner. The result of RT-PCR analysis revealed that naringin down-regulated the mRNA expression levels of BCL-2 and up-regulated BAX, caspase-3 and cytochrome C. In addition, naringin significantly reduced the bone resorption area in vitro. These findings suggest that naringin promotes the apoptosis of osteoclasts by regulating the activity of the mitochondrial apoptosis pathway and prevents OVX-induced osteoporosis in rats.
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PMID:Naringin prevents ovariectomy-induced osteoporosis and promotes osteoclasts apoptosis through the mitochondria-mediated apoptosis pathway. 2518 44

BACKGROUND Facet joint degeneration (FJD) is one of the common causes of low back pain (LBP), and estrogen deficiency is one of the triggers for FJD. Calcitonin may possess the potential for treating osteoarthritis, but to date the hormone has not been studied in the treatment of FJD. Therefore, the aim of this study was to investigate the effects of salmon calcitonin (sCT) on FJD induced by estrogen deficiency after ovariectomy (OVX). MATERIAL AND METHODS Thirty female Sprague-Dawley rats were randomly assigned to 3 groups: the OVX group received bilateral OVX, the OVX + sCT group received subcutaneous administration of sCT (16 IU/kg/2 days) following bilateral OVX, and the Sham group received sham surgery. All rats were euthanized at 12 weeks post-OVX. Serum COMP level, cartilage degradation, and subchondral bone micro-architecture were evaluated. RESULTS sCT relieved cartilage surface lesions, reduced histological score, and significantly increased cartilage thickness. The OVX + sCT group exhibited significantly increased expression of aggrecan, as well as significantly decreased levels of ADAMTS-4, MMP-13, and caspase-3. The results of micro-computed tomography analysis revealed that the OVX + sCT group exhibited higher BMD, BV/TV, and Tb.Th values but a lower Tb.Sp value than that of the OVX group. Serum COMP concentrations were significantly correlated with histological score and cartilage thickness. CONCLUSIONS sCT can inhibit the progression of FJD in OVX rats, which is attributed to its inhibitory effects on cartilage metabolism imbalance, chondrocyte apoptosis, and subchondral bone remodeling. Serum COMP has diagnostic potential for FJD.
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PMID:Salmon Calcitonin Attenuates Degenerative Changes in Cartilage and Subchondral Bone in Lumbar Facet Joint in an Experimental Rat Model. 2974 28