کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2597599 1132592 2007 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Mechanisms of inhibited liver tissue repair in toxicant challenged type 2 diabetic rats
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Mechanisms of inhibited liver tissue repair in toxicant challenged type 2 diabetic rats
چکیده انگلیسی

Liver injury initiated by non-lethal doses of CCl4 and thioacetamide (TA) progresses to hepatic failure and death of type 2 diabetic (DB) rats due to failed advance of liver cells from G0/G1 to S-phase and inhibited tissue repair. Objective of the present study was to investigate cellular signaling mechanisms of failed cell division in DB rats upon hepatotoxicant challenge. In CCl4-treated non-diabetic (non-DB) rats, increased IL-6 levels, sustained activation of extracellular regulated kinases 1/2 (ERK1/2) MAPK, and sustained phosphorylation of retinoblastoma protein (p-pRB) via cyclin D1/cyclin-dependent kinase (cdk) 4 and cyclin D1/cdk6 complexes stimulated G0/G1 to S-phase transition of liver cells. In contrast to the non-DB rats, CCl4 administration led to lower plasma IL-6, decreased ERK1/2 activation, lower cyclin D1, and cdk 4/6 expression resulting in decreased p-pRB and inhibition of liver cell division in the DB rats. Furthermore, higher TGFβ1 expression and p21 activation may also contribute to decreased p-pRB in DB rats compared to non-DB rats. Similarly, after TA administration to DB rats, down-regulation of cyclin D1 and p-pRB leads to markedly decreased advance of liver cells from G0/G1 to S-phase and tissue repair compared to the non-DB rats. Hepatic ATP levels did not differ between the DB and non-DB rats obviating its role in failed tissue repair in the DB rats. In conclusion, decreased p-pRB may contribute to blocked advance of cells from G0/G1 to S-phase and failed cell division in DB rats exposed to CCl4 or TA, leading to progression of liver injury and hepatic failure.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 232, Issue 3, 11 April 2007, Pages 200–215
نویسندگان
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