کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5863007 1133789 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Manganese-induced toxicity in normal and human B lymphocyte cell lines containing a homozygous mutation in parkin
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Manganese-induced toxicity in normal and human B lymphocyte cell lines containing a homozygous mutation in parkin
چکیده انگلیسی

Mutations in the parkin gene are linked to development of juvenile onset of Parkinson's disease and recent studies have reported that parkin can protect against increased oxidative stress and mitochondrial dysfunction caused by a variety of oxidative and toxic insults. Overexpression of parkin has also been reported to selectively protect dopaminergic neurons from Mn toxicity. Accordingly, in this paper we compare the effect that mutations in parkin have on Mn toxicity and associated apoptotic signals in normal and human B lymphocyte cell lines containing a homozygous mutation in the gene. Results of these studies reveal that Mn toxicity was similar in both control and mutant parkin lymphocyte cells indicating that cell death caused by Mn was not altered in cells devoid of parkin activity. In contrast, Mn did inhibit mitochondrial function to a greater extent in cells devoid of active parkin as indicated by a decrease in ATP production although mitochondrial membrane potential was essentially unaffected. Consistent with inactive parkin influencing the Mn response is the observation of increased activity in the down-stream apoptotic signal, caspase 3. In summary, results reported in this paper demonstrate that mutations in parkin can lead to functional changes in potential signaling processes known to provoke Mn toxicity. The selectivity and magnitude of this response, however, does not necessarily lead to cell death in lymphocytes which are devoid of dopamine.

► Mn-induced toxicity was not different between control and a lymphocyte cell line lacking active parkin. ► Mn-induced oxidative stress markers were increased in the lymphocyte cell line lacking active parkin. ► Mn-induced ATP levels were decreased greater in the lymphocyte cell line lacking active parkin.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology in Vitro - Volume 26, Issue 7, October 2012, Pages 1143-1149
نویسندگان
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