Role of α<sub>1</sub>-Acid Glycoprotein in Therapeutic Antifibrotic Effects of Imatinib with Macrolides in Mice

Azuma, Momoyo; Nishioka, Yasuhiko; Aono, Yoshinori; Inayama, Mami; Makino, Hideki; Kishi, Jun; Shono, Masayuki; Kinoshita, Katsuhiro; Uehara, Hisanori; Ogushi, Fumitaka; Izumi, Kiyotaka; Sone, Saburo

doi:10.1164/rccm.200702-178oc

Cited by 52 publications

(42 citation statements)

References 36 publications

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“…Nem árt meggondolni az orozom.-glikoziláció rendkívüli változatosságát nemcsak kóros viszonyok kö-zött, hanem élettani helyzetben is. Az ösztradiol számára két kötőhely is rendelkezésre áll a molekulában [35,36]. Az elmondottak alapján mégis meglepő, hogy az orozom.…”

Section: Táblázatunclassified

A heterogén glikoproteinszerkezetek biológiai szerepe

Jakab

2016

Orvosi Hetilap

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A fehérjemolekulához kovalens kötéssel kötődő szénhidrát-molekulák glikoproteineket alkotnak. A fehérjelánchoz különböző mennyiségű és összetételű szénhidrát-molekulák kapcsolódhatnak változó sorrendben és mennyiségben. Ha a fehérjemaghoz kötötten acidikus uronsavat, SO 4 -gyököt lehet találni, akkor proteoglikánokról vagy kevésbé helyesen glükózaminoglikánokról szólunk. Az élővilágban fellelhetők polimannanszerkezetek. A glikoproteinek acidikus uronsav vagy szulfatált glikózaminoglikánokat csak kivételszerűen tartalmaznak. Mind a szöveti, sejtes és mát-rixszerkezetek, mind a humán "szérumfehérjék" valójában döntően glikoproteinek. A glikoprotein fogalom haszná-lata a klinikai orvostudományban máig is csak nagyon gyéren fordul elő, pedig a nem adekvát szófogalom-használat nemcsak nem helyénvaló, hanem egyúttal szemléletbeli zavarral is járhat. A közlemény ezt a gyakorlatot kívánja javí-tani, figyelembe véve, hogy ma már a "glikobiológia" szinte önálló tudományágként funkcionál. A szerkezeti sajátos-ságok összesítése mellett a közlemény ennek fontos, gyakorlati következményeit kívánja pótolni, funkcionális és konkrét klinikai vonatkozásait összefoglalni. Így kerül sor a glikoproteinek szerkezeti és biológiai tulajdonságainak bemutatására, hangsúlyt helyezve a klinikai fontosságra. A közlemény kiemeli a kóros struktúra és funkció klinikai vonatkozásait. Az orozomukoidot és a szérum-immunoglobulinokat a szerző külön fejezetben tárgyalja. Orv. Hetil., 2016, 157(30), 1185-1192.Kulcsszavak: protein, glikoprotein, szerkezet, funkció, klinikai jelentőség Biological role of heterogeneous glycoprotein structuresCarbohydrate molecules connected mostly with covalent junctions to protein chains are called glycoproteins. These carbohydrate molecules are attached to the protein core in different qualities and order. When the protein core is connected with acidic components such as uronic acid or SO 4 radicals, they are called proteoglycans. The currently used name "glycosaminoglycan" in this case is not entirely correct. In the living world polymannane structures occur, too. Glycoproteins do not only exceptionally hold acidic groups but they have neuraminic acid derivatives. Tissue, cellular and matrix structures, and mostly all serum "proteins" are mainly glycoproteins. In the everyday clinical practice glycoproteins are mentioned as proteins. Nevertheless, the inadequate use of the concept may cause errors in the attitudes, too. This paper aims to correct this notion, because the term of "glycobiology" has already been expanded to be an independent scientific field. The practical clinical consequences of recent knowledge in this field are also summarized including novel findings on glycoprotein structures and functions. The importance of the quantity of carbohydrates, and their structural arrangements are also presented. In short, significance of glycoproteincarbohydrate structures, as well as their physiological and pathological roles are reviewed in order to introduce the field of "glycobiology". Orosomucoid and immunoglo...

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Section: Táblázatunclassified

A heterogén glikoproteinszerkezetek biológiai szerepe

Jakab

2016

Orvosi Hetilap

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“…The C57BL/6 and MLg lung fibroblasts (8!10 3 cells per well) were cultured in 96-well flat-bottomed tissue plates in RPMI1640 supplemented with 10% FBS, and then serum-starved in medium containing 0.1% FBS overnight (19,20,22) [19,27,28]. Next, the cells were treated with various doses (1 to 200 ng/ml) of CCN6, and PDGF-BB (10 ng/ml) as a positive control for 72 hours, and labeled with 3 H -thymidine deoxyribose (TdR) (6.7 Ci/mmol ; Amersham Corp., Arlington Heights, IL) at 1 μCi/ well for the final 18 hours.…”

Section: Proliferation Assaymentioning

confidence: 99%

“…To detect CCN6 expression in BLMtreated lung tissue, lung tissues were homogenized and lysed in RIPA Buffer (Pierce, Rockford, IL). Their protein concentrations were determined using the Bradford protein assay (Sigma-Aldrich) (19,20). Immunoprecipitation was performed using 500 μg of total proteins, and immune complexes were recovered with Protein G-Sepharose beads (Zymed Laboratories, South San Francisco, CA) (19,20).…”

Section: Western Blot Analysismentioning

confidence: 99%

“…Their protein concentrations were determined using the Bradford protein assay (Sigma-Aldrich) (19,20). Immunoprecipitation was performed using 500 μg of total proteins, and immune complexes were recovered with Protein G-Sepharose beads (Zymed Laboratories, South San Francisco, CA) (19,20). For Western blotting analysis, immunoprecipitates or 30 μg of total protein were resolved by SDS-PAGE (Bio -Rad, Hercules, CA), and the proteins were then transferred to PVDF membranes (Atto, Tokyo, Japan).…”

Section: Western Blot Analysismentioning

confidence: 99%

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CCN6 as a profibrotic mediator that stimulates the proliferation of lung fibroblasts via the integrin .BETA.1/focal adhesion kinase pathway

et al. 2011

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“…In addition, failure of imatinib treatment to prevent lung fibrosis in a mouse model of bleomycin lung fibrosis was caused by AGP. Furthermore, in human patients with idiopathic pulmonary fibrosis half of patients had circulating levels of AGP high enough to lower imatinib serum levels below that needed to inhibit PDGFR in vitro (49).…”

Section: Are Animal Models Useful To Predict Clinical Responses In Momentioning

confidence: 99%

Tyrosine Kinase Inhibitors in the Treatment of Systemic Sclerosis: From Animal Models to Clinical Trials

Iwamoto

Distler

2010

Curr Rheumatol Rep

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Efficient antifibrotic therapies are not available for patients with systemic sclerosis (SSc). This review summarizes the current preclinical and clinical evidence for imatinib and related tyrosine kinase inhibitors as potential antifibrotic therapies for SSc and other fibrotic diseases. In experimental models of SSc, imatinib, nilotinib, and dasatinib demonstrated strong antifibrotic effects. Imatinib not only prevented fibrosis in the bleomycin-induced model of dermal fibrosis and the tight skin mouse-1 model but also reduced established fibrosis in a modified bleomycin model. Open-label, proof-of-concept trials in SSc showed moderate effects on skin fibrosis, biological measures of skin fibrosis, and lung fibrosis compared with baseline measures. However, whether this reflects the natural course of the disease or is a result of treatment effects is unclear and needs to be analyzed in larger, multicenter, randomized, placebo-controlled trials. Toxicity is expected from cancer trials with frequent mild to moderate adverse events. This review summarizes the current preclinical and clinical evidence for imatinib and related tyrosine kinase inhibitors as potential anti-fibrotic therapies in SSc and other fibrotic diseases. Tyrosine Kinase Inhibitors in the Treatment of Systemic Sclerosis: From Animal Models to Clinical Trials

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Role of α₁-Acid Glycoprotein in Therapeutic Antifibrotic Effects of Imatinib with Macrolides in Mice

Abstract: AGP is an important regulatory factor modulating the ability of imatinib to prevent pulmonary fibrosis in mice, and combined therapy with imatinib and EM or CAM might be useful for treatment of pulmonary fibrosis.

Cited by 52 publications

References 36 publications

A heterogén glikoproteinszerkezetek biológiai szerepe

A heterogén glikoproteinszerkezetek biológiai szerepe

CCN6 as a profibrotic mediator that stimulates the proliferation of lung fibroblasts via the integrin .BETA.1/focal adhesion kinase pathway

Tyrosine Kinase Inhibitors in the Treatment of Systemic Sclerosis: From Animal Models to Clinical Trials

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Role of α1-Acid Glycoprotein in Therapeutic Antifibrotic Effects of Imatinib with Macrolides in Mice

Abstract: AGP is an important regulatory factor modulating the ability of imatinib to prevent pulmonary fibrosis in mice, and combined therapy with imatinib and EM or CAM might be useful for treatment of pulmonary fibrosis.

Cited by 52 publications

References 36 publications

A heterogén glikoproteinszerkezetek biológiai szerepe

A heterogén glikoproteinszerkezetek biológiai szerepe

CCN6 as a profibrotic mediator that stimulates the proliferation of lung fibroblasts via the integrin .BETA.1/focal adhesion kinase pathway

Tyrosine Kinase Inhibitors in the Treatment of Systemic Sclerosis: From Animal Models to Clinical Trials

Contact Info

Product

Resources

About

Role of α₁-Acid Glycoprotein in Therapeutic Antifibrotic Effects of Imatinib with Macrolides in Mice