Expression of Bcl-2 family proteins in thyrocytes from young patients with immune and nonimmune thyroid diseases.
The Bcl-2 family proteins that control homeostasis of cells play an important role in apoptosis. This group consists of antiapoptotic (Bcl-2, Bcl-XL) and proapoptotic (Bcl-2 associated protein X, Bax; B-cell homologous antagonist/killer, Bak) molecules. In the thyroid, abnormal apoptotic activity may be involved in a variety of diseases such as autoimmune thyroid diseases. The aim of the current study was to estimate the expression of pro- and antiapoptotic proteins in thyroid tissues from young patients with Graves' disease (GD), nontoxic nodular goiter and toxic nodular goiter using Western Blot and immunohistochemistry. Identification of the antiapoptotic Bcl-2 and Bcl-XL molecules in the thyrocytes revealed higher expression of both proteins in patients with GD (assessed as +++/++ and ++/+, respectively). In adolescents with toxic and nontoxic nodular goiter, this expression was lower (Bcl-2 ++/+ , ++/+; Bcl-XL +, +). The tissue material was additionally subjected to Western Blot analysis, which in GD patients showed the presence of Bcl-2 and Bcl-XL in one band p26 kDa. In patients with toxic and nontoxic nodular goiter, the intensity of expression for these two antiapoptotic proteins was lower (referred to band 26 kDa for Bcl-2 and Bcl-XL). Identification of the proapoptotic proteins Bax and Bak revealed their predominance in thyrocytes of GD patients (+, ++/+, respectively) as compared to patients with toxic and nontoxic nodular goiter (0/+, 0/+ for Bax and 0/+, 0/+ for Bak). In GD patients, Western Blot analysis showed Bax expression in one band 21 kDa and Bak in two bands p50, p24 kDa. In patients with nodular goiter, the degree of expression of both proapoptotic proteins was lower and referred to band 21 kDa for Bax (toxic and nontoxic goiter) and 24 kDa for Bak (toxic goiter only). Patients with GD showed a statistically significant correlation between Bcl-2 expression and antibodies against receptor for thyroid stimulating hormone (R = 0.47, p < 0.03); however, such a correlation was not observed in patients with nodular goiter. In conclusion, our findings suggest that the changes in the expression of regulatory proteins of the Bcl-2 family in the thyroid follicular cells indicate the involvement of apoptosis in the pathogenesis of GD.
Bossowski
A
A
Second Department of Children's Diseases, Medical University of Białystok, Warsaw, Poland. abossowski@hotmail.com
Czarnocka
B
B
Bardadin
K
K
Urban
M
M
Niedziela
M
M
Dadan
J
J
D000293:Adolescent; D000328:Adult; D013956:Antithyroid Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D015153:Blotting, Western; D002648:Child; D005260:Female; D006044:Goiter, Nodular / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006111:Graves Disease / Q000097:blood / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008713:Methimazole / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D013956:Antithyroid Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D014284:Triiodothyronine; D008713:Methimazole; D013972:Thyrotropin; D013974:Thyroxine