کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5832670 | 1122606 | 2014 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Enhanced diacylglycerol production by phospholipase D activation is responsible for abnormal increase in concanavalin A cap formation in polymorphonuclear leukocytes from Chediak-Higashi syndrome (beige) mice
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کلمات کلیدی
Concanavalin APEtOHdiC81-Oleoyl-2-acetyl-sn-glycerolN-SmaseA-SMasesn-1,2-dioctanoylglycerolPIP2Chediak–Higashi syndromeOAGFITCHBSSCHSnatural killer - (سلول های) کشنده طبیعی2,3-DPG - 2،3-DPG2,3-diphosphoglycerate - 2،3-دی فسفوگلسراتacidic sphingomyelinase - اسفنجومیلیناز اسیدیneutral sphingomyelinase - اسپینگومییلیناز خنثیphosphatidic acid - اسید فسفاتیدیکCon A - با Adiacylglycerol - دیسیل گلیسیرینDAG - روزphosphatidylcholine - فسفاتیدیل کولینphosphatidylethanol - فسفاتیدیلنتانولfluorescein isothiocyanate - فلوئورسین ایسوتیوسیاناتHank's balanced salt solution - محلول نمک متعادل هانکFAN - پنکه
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
We previously reported that enhanced ceramide production induces calpain-mediated proteolysis of protein kinase C (PKC) in leukocytes from Chediak-Higashi syndrome (CHS). In the present study, we demonstrated that phospholipase D (PLD) inhibitors ameliorated abnormal increases in concanavalin A (Con A) cap formation in polymorphonuclear leukocytes (PMNs) from beige mouse, an animal model of CHS. PLD activity in PMNs from beige mice enhanced at 30 to 60Â s after Con A stimulation. In Con A-stimulated beige PMNs, both neutral sphingomyelinase (N-SMase) and acidic sphingomyelinase (A-SMase) activities enhanced, and ceramide levels are also increased. We found that ceramide levels were reversed by the treatment of beige PMNs with propranolol which inhibits phosphatidic acid phosphohydrolase. In addition, we showed that diacylgycerol (DAG) analogs enhance both N-SMase and A-SMase activities in PMNs from normal mice. We subsequently examined the association of CHS1 with PLD, and showed that expression of a truncated mutant of CHS1 in 293T cells induced abnormally rapid activation of PLD after phorbol ester stimulation. Moreover, we showed that specific inhibitors of 14-3-3 proteins, which interact with CHS1/LYST and bind PKC, did not affect abnormal increases in Con A cap formation in beige PMNs. These results suggest that the enhanced DAG production via the PLD pathway is associated with abnormal increases in Con A cap formation in beige PMNs, and that CHS1 may be involved in the regulation of PLD activity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 21, Issue 1, July 2014, Pages 193-199
Journal: International Immunopharmacology - Volume 21, Issue 1, July 2014, Pages 193-199
نویسندگان
Hirotake Kasai, Fuminori Tanabe,