کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2524496 | 1119574 | 2012 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Ablation of the ATP-binding cassette transporter, Abca2 modifies response to estrogen-based therapies
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کلمات کلیدی
PBSEMPNOSPFAABCABC transporter - ABC حمل کنندهHET - ITEstramustine phosphate - استراستین فسفاتEstramustine - استروماستینEstrogen - استروژنBrdU - بروموداکسی اوریدینbromodeoxyuridine - برومودسوویریدینATP-binding cassette transporter - حمل کننده کاسه اتصال ATPGastrointestinal - دستگاه گوارشknockout - ناکاوتwild type - نوع وحشیnitric oxide synthase - نیتریک اکسید سنتازheterozygous - هتروزیگوتparaformaldehyde - پارافرمالدهیدProstate - پروستات
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
تومور شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The ATP-binding cassette transporter 2 (ABCA2) is an endolysosomal protein expressed in oligodendrocytes and Schwann cells, prostate, ovary and macrophages. In cell cultures, ABCA2 over-expression has been linked with resistance to the anticancer agent, estramustine phosphate (EMP; a nor-nitrogen mustard conjugate of estradiol). The present study shows that Abca2 knockout (KO) mice have greater sensitivity to a variety of side effects induced by EMP treatment. Chronic EMP (12Â ÃÂ 100Â mg/kg body weight) produced mortality in 36% of KO mice, but only 7% of age-matched wild type (WT). Side effects of the drug were also more prevalent in the KO mouse. For example, during the first week of EMP treatments, 67% of KO males (compared to 6% of WT males) responded with episodic erectile events. In WT mice, ABCA2 protein localized within pene corpuscles, (which rely on modified Schwann cells for amplification of tactile signals) suggesting that the transporter may function in the erectile process. Endothelial nitric oxide synthase (eNOS; a source of nitric oxide during erectile response) levels were similar in WT and KO male penile tissue. Treatment with 100Â mg/kg EMP (once daily for four days) elevated serum estradiol and estrone in both WT and KO. However, the circulating levels of these estrogens were higher in KO mice implying a reduced plasma clearance of estrogens as a consequence of ABCA2 ablation. Consistent with the pro-convulsant effects of estrogens, KO mice also displayed an increased incidence of seizures following EMP (14% vs. 0%). Taken together, these data indicate that ABCA2 deficiency renders mice more sensitive to EMP treatment-induced effects implying that the transporter has a role in regulating EMP transport and/or metabolism.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biomedicine & Pharmacotherapy - Volume 66, Issue 6, September 2012, Pages 403-408
Journal: Biomedicine & Pharmacotherapy - Volume 66, Issue 6, September 2012, Pages 403-408
نویسندگان
Jody T. Mack, Carol B. Brown, Tracy E. Garrett, Joachim D. Uys, Danyelle M. Townsend, Kenneth D. Tew,