Necroptosis mediated by receptor interacting protein kinase 3 as critical players in experimental congenital hypothyroidism related neuronal damage

OBJECTIVE: Congenital hypothyroidism (CH) is literally described as congenital thyroid hormone imperfection. The primary objective of this research was to reveal the possible relation between receptor-acting protein kinase 3 (RIPK3) activity and neuronal damages in rat pups with CH. In addition, we evaluated the favorable impacts of 3.6-dibromo-α-([phenylamino] methyl)-9H-carbazole-9-ethanol (P7C3) reducing RIPK3 activity.
METHODS: Adult rats were accordingly assigned into four groups: Group 1, which is called congenital hypothyroid; Group 2, which is called congenital hypothyroid administered P7C3; Group 3, called CH administered P7C3 and L-thyroxine; and Group 4, control group. RIPK3 level in plasma concentration and its expression in tissue was determined in all groups.
RESULTS: Increased RIPK3 expressions were detected as high in the CH group when it is compared to the control group. Furthermore; the expressions in neuronal cytoplasm were found similar among Groups II and III. RIPK3 expressions in those two groups were relatively higher than in the control group. Most reacted parts of the brain were especially Purkinje cells in the cerebellum.
CONCLUSION: It is concluded that there is excellent parallelism among damaged neurons and high RIPK3 activity in CH pathogenesis. P7C3 compounds may have a safeguarding impact on CH due to decreasing RIPK3 activity.

Necroptosis mediated by receptor interacting protein kinase 3 as critical player in experimental congenital hypothyroidism related neuronal damage

Objektif: Konjenital hipotiroidizm (KH) doðuþtan tiroid hormonu kusuru olarak tanýmlanmaktadýr. Bu araþtýrmanýn birincil amacý, KH'li sýçan yavrularýnda RIPK3 aktivitesi ile nöronal hasarlar arasýndaki olasý iliþkiyi ortaya çýkarmaktýr. Yanýsýra 3,6-Dibromo-α - [(fenilamino)metil]-9H-karbazol-9-etanolün (P7C3) RIPK3 aktivitesini azaltan etkiler incelendi.
Materyal ve Metod: Eriþkin sýçanlar dört gruba ayrýldý: Grup 1, konjenital hipotiroidi; Grup 2, konjenital hipotiroid uygulanan P7C3; Grup 3, KH uygulanan P7C3 ve L-tiroksin; Grup 4, kontrol grubu. Plazma konsantrasyonundaki ve dokudaki RIPK3 düzeyi ve gen ekspresyon seviyesi tüm gruplarda incelendi.
Bulgular: Kontrol grubu ile karþýlaþtýrýldýðýnda CH grubunda artan RIPK3 ekspresyonlarý yüksek olarak bulundu. Ayrýca; Nöronal sitoplazmadaki ifadeler grup II ve III arasýnda benzer bulundu. Bu iki gruptaki RIPK3 ifadeleri, kontrol grubuna göre nispeten daha yüksekti. Beynin en çok tepki veren kýsýmlarý, özellikle serebellumdaki Purkinje hücreleriydi.
Sonuç: KH patogenezinde hasarlý nöronlar arasýnda mükemmel paralellik ve yüksek RIPK3 aktivitesi olduðu sonucuna varýldý. P7C3 bileþikleri, RIPK3 aktivitesinin azalmasý nedeniyle KH üzerinde koruyucu bir etkiye sahip olabilir. (NCI-2021-3-11)