Cell necrosis and apoptosis are differentially regulated during goitre development and iodine-induced involution

Abstract

Necrosis and apoptosis coexist in the thyroid during goitre development and involution, but little is known about their respective causes. To test the possible role of free radicals, we analysed separately necrosis and apoptosis in male Wistar rats with depressed or normal antioxidant protection. Vitamin E-deficient and -sufficient rats were made goitrous with perchlorate in drinking water; involution was induced by repeated injection of NaI, without or with methimazole. Increase of thyroid malondialdehyde concentration and decrease of glutathione peroxidase activity confirmed the depressed antioxidant protection in vitamin E-deficient rats. Plasma thyroxine and TSH levels were not modified. Necrosis (swollen cells) and apoptosis (pyknotic cells) were quantified on histological sections. In vitamin E-sufficient rats, dead cells were very rare in control thyroids, increased 3-fold in goitre and still further during involution.Necrotic epithelial cells predominated in the goitre and their number declined after iodide supplementation, without or with methimazole. In contrast, the number of apoptotic cells and the caspase-3 activity were increased in goitre and further increased after involution, with twothirds of pyknotic cells being observed in the interstitium. Apoptosis was prevented by methimazole. Vitamin E deficiency significantly increased total cell death and epithelial cell necrosis and induced the occurrence of much cell debris in the follicular lumen during involution, with no modification of the apoptotic reaction. These results show that the type of cell death is differentially regulated during goitre development and involution: necrosis is related to the oxidative status of the cells, while apoptosis comes with iodine-induced involution.

Signaling pathways involved in the antiproliferative effect of molecular iodine in normal and tumoral breast cells: evidence that 6-iodolactone mediates apoptotic effects

“…In the present work, we confirmed the increase in BAX and the nuclear translocation of AIF, but we also detected the activated caspase-7 subunit of 17 kDa, as well as PARP1 cleavage, indicating the possibility that more than one pathway was activated by I 2 . These data agreed with a previous report showing that during iodine-induced goiter involution, the triggering of apoptosis is also mediated by caspases (Mutaku et al 2002). Thus, we propose that in tumoral cells, at low concentrations I 2 binds to AA, which is present at an elevated concentration, and forms 6-IL, which in turn activates PPAR, triggering BAX/caspase-dependent apoptosis.…”

Oxidative Stress and Antioxidant Status in Hypo- and Hyperthyroidism

“…Because of its great toxicity, H2O2 synthesis must always remain in adequation with the hormonal synthesis and strictly contained at the apical pole of the cell. Thyrocytes possess various enzymatic systems, such as GPx, catalase, superoxide dismutases, and peroxiredoxins that contribute to limit cellular injuries when H2O2 or other ROS are produced in excess [155,156,157].…”

Minimal oxidative load: a prerequisite for thyroid cell function

“…To preserve cell integrity, several protective systems against ROS, such as peroxiredoxins (PRDX), catalase, and glutathione peroxidases are heavily expressed and active in thyrocytes. Thus, PRDX5 and glutathione peroxidase are increased in goitrous thyroids, both in human and rodents (Mano et al 1997, Mutaku et al 2002, Gerard et al 2005, Poncin et al 2008a. Cells can rely on various antioxidant tools to maintain the oxidative stress (OS) in strict limits to avoid OS becoming eventually harmful.…”