کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9436534 | 1615694 | 2005 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cytoplasmic and intra-nuclear binding of gentamicin does not require endocytosis
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کلمات کلیدی
PBSFBSMDCKn.a.PIP2LLC-PK1Aminoglycoside - آمینوگلیکوزیدTexas red - تگزاس قرمزDrug uptake - جذب مواد مخدرGentamicin - جنتامایسینnumerical aperture - دیافراگم عددیfetal bovine serum - سرم جنین گاوcytoplasmic - سیتوپلاسمیکphosphatidylinositol-4,5-bisphosphate - فسفاتیدیلینستول-4،5-بیسفسفاتPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافری
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
سیستم های حسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Understanding the cellular mechanism(s) by which the oto- and nephrotoxic aminoglycoside antibiotics penetrate cells, and the precise intracellular distribution of these molecules, will enable identification of aminoglycoside-sensitive targets, and potential uptake blockers. Clones of two kidney cell lines, OK and MDCK, were treated with the aminoglycoside gentamicin linked to the fluorophore Texas Red (GTTR). As in earlier reports, endosomal accumulation was observed in live cells, or cells fixed with formaldehyde only. However, delipidation of fixed cells revealed GTTR fluorescence in cytoplasmic and nuclear compartments. Immunolabeling of both GTTR and unconjugated gentamicin corresponded to the cytoplasmic distribution of GTTR fluorescence. Intra-nuclear GTTR binding co-localized with labeled RNA in the nucleoli and trans-nuclear tubules. Cytoplasmic and nuclear distribution of GTTR was quenched by phosphatidylinositol-bisphosphate (PIP2), a known ligand for gentamicin. Cytoplasmic and nuclear GTTR binding increased over time (at 37 °C, or on ice to inhibit endocytosis), and was serially competed off by increasing concentrations of unconjugated gentamicin, i.e., GTTR binding is saturable. In contrast, little or no reduction of endocytotic GTTR uptake was observed when cells were co-incubated with up to 4 mg/mL unconjugated gentamicin. Thus, cytoplasmic and nuclear GTTR uptake is time-dependent, weakly temperature-dependent and saturable, suggesting that it occurs via an endosome-independent mechanism, implicating ion channels, transporters or pores in the plasma membrane as bioregulatory routes for gentamicin entry into cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Hearing Research - Volume 204, Issues 1â2, June 2005, Pages 156-169
Journal: Hearing Research - Volume 204, Issues 1â2, June 2005, Pages 156-169
نویسندگان
Sigrid E. Myrdal, Katherine C. Johnson, Peter S. Steyger,