Biomedical subjects

Pentti Tuohimaa

Publications and source records attributed to Pentti Tuohimaa.

40 records · Page 3Linked to original sources

PubMed2002

Suppression of immunoreactive macrophages in atheromatous lesions of rabbits by clodronate.

Bisphosphonates inhibit the development of experimental atherosclerosis and decrease the intima-media thickness of human carotid artery. Since arterial macrophages have a key role in atherogenesis, we studied whether clodronate, an antiatherogenic bisphosphonate, will suppress the appearance of macrophages generated by atheromatous process in the rabbit aorta. The atherosclerosis was caused in rabbits by means of a high-cholesterol (1%) diet, and the animals were treated simultaneously with saline (n = 11) or 25 mg/kg of clodronate disodium (n= 12) intravenously twice a week for 6 to 12 weeks. The cholesterol diet for 6 weeks caused no visible atheromatous plaques in the aorta, but feeding for 6 more weeks produced progressively atheromatous lesions. Immunohistochemistry with specific antimacrophage antibody showed an intensive accumulation of macrophages in the subendothelial layer of the aorta in cholesterol-fed rabbits treated with saline or clodronate for 6 weeks. In the aorta of rabbits treated with cholesterol diet + saline for 12 weeks, the area of immunoreactive macrophages extended from the internal elastic lamina up to the luminal surface of the aorta. However, far less immunoreactive macrophages were present in the atheromatous regions of the aorta of rabbits medicated with clodronate for 12 weeks; in the clodronate-treated animals the macrophages were located closer to the luminal surface of the aorta than in controls on saline. No atheromatous lesions and macrophages appeared in the aorta of rabbits on standard diet (n = 7). The results suggest that clodronate suppresses the appearance of cholesterol-phagocyting macrophages in arterial walls during atherogenesis.

Animals↗

PubMed2002

Progestin upregulates G-protein-coupled receptor 30 in breast cancer cells.

A differential display method was used to study genes the expression of which is altered during growth inhibition induced by medroxyprogesterone acetate (MPA). A transcript of G-protein-coupled receptor 30 (GPR30) was upregulated by MPA in estrogen-treated MCF-7 breast cancer cells. Northern-blot analysis showed a progestin-specific primary target gene, which was enhanced by progesterone and different progestins, but not by dihydrotestosterone or dexamethasone, and which was abrogated by antiprogestin RU486. The dose-dependent and time-dependent increase in GPR30 mRNA expression correlated with MPA-induced growth inhibition in MCF-7 cells. Additionally, GPR30 upregulation by progestin correlated with growth inhibition when a comparison was made between different breast cancer cell lines. The ERK1/ERK2 pathway is capable of inducing progesterone receptor-dependent and ligand-dependent transcription. Thus we sought to establish whether different MAPK pathway inhibitors affect progestin-induced GPR30 mRNA regulation. The regulation of GPR30 was independent of ERK pathway activation, but the p38 pathway inhibitor induced GPR30 expression, which suggested a potential gene regulation pathway. These data demonstrate a new progestin target gene, the expression of which correlates with growth inhibition.

Breast Neoplasms↗

PubMed2002

Comparative distribution of the mammalian mediator subunit thyroid hormone receptor-associated protein (TRAP220) mRNA in developing and adult rodent brain.

TRAP220 (thyroid hormone receptor-associated protein) is a recently cloned nuclear receptor coactivator, which interacts with several nuclear receptors in a ligand-dependent manner and stimulates transcription by recruiting the TRAP mediator complex to hormone responsive promoter regions. TRAP220 has been shown to interact with thyroid hormone receptors, vitamin D receptors, peroxisome proliferator-activated receptors, retinoic acid receptors and oestrogen receptors. Thyroid hormone and retinoic acid play very important roles in brain development and they also influence adult brain. Using in situ hybridization we have examined expression of TRAP220 mRNA in the central nervous system during development and in adult rat and mouse brain. Expression of TRAP220 was seen already during early embryonic development in the epithelium of neural tube at E9 in mouse and at E12 in rat. At later stages of development the strongest signal was seen in different layers of cerebral neocortex, external germinal layer of cerebellum, differentiating fields of hippocampus and neuroepithelium, and a moderate signal was detected in basal ganglia, different areas of diencephalon and midbrain. In adult rat brain the signal was more restricted than during development. TRAP220 expression occurred mostly in the granular layer of cerebellar cortex, piriform cortex and hippocampal formation. The signal was found predominantly in neurons. Our work supports the assumption that TRAP220 plays an important role in growth and differentiation of central nervous system and may have a function in certain areas of adult brain.

Animals↗

PubMedDate not supplied

Abnormal behavioral organization of grooming in mice lacking the vitamin D receptor gene.

Vitamin D is a steroid hormone with several important functions in the nervous system. Numerous human and animal data link alterations in the vitamin D system to various behavioral disorders. Grooming is an important element of rodent behavior with a general pattern of cephalocaudal progression (paw licking - nose/face wash - body wash - tail/genitals wash). Here we studied whether genetic ablation of vitamin D nuclear receptors (VDR) in mice may be associated with altered behavioral sequencing of grooming. Overall, VDR null mutant mice showed abnormal grooming, including a higher percentage of "incorrect" transitions and longer duration of "incorrect" grooming (contrary to the cephalocaudal progression); a higher percentage of interrupted grooming bouts; and the atypical regional distribution of grooming (more leg grooming, less body and tail/genitals grooming), compared to their wild-type controls. Grooming of heterozygous mice was similar to the wild-type group, indicating that abnormal grooming patterning is inherited as a recessive. In contrast, behavioral sequencing of another complex behavior (mating with a female) was unaltered in all three genotypes, suggesting grooming-specific abnormal sequencing in these mutant mice. Our results suggest that a neurosteroid vitamin D and VDR may play an important role in controlling sequencing of grooming in mice, and further confirm the important role of the vitamin D system and VDR in the regulation of behavior.

Animals↗