Using rat model of hypothyroidism-induced neuronal apoptosis, selleck kinase inhibitor we provide evidence for anti-apoptotic role of omega 3 FAs during cerebellar development. omega 3 FAs were supplemented as a mixture of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to pregnant and lactating rats, and primary hypothyroidism was induced by administering methimazole. The cerebella from postnatal day 16 (d16) pups were isolated, and studies on apoptosis were conducted. We observed that omega 3 FA-supplementation significantly reduced DNA fragmentation and caspase-3 activation in developing cerebellum of hypothyroid pups. The protection provided
by omega 3 FAs was associated with their ability to prevent increases in the level of pro-apoptotic basal cell lymphoma protein-2 (Bcl-2)-associated X protein (Bax) in the cerebellum during thyroid hormone (TH) deficiency. omega AG-881 solubility dmso 3 FAs increased the levels of anti-apoptotic proteins like Bcl-2 and Bcl-extra large (Bcl-X(L)), known to be repressed in
hypothyroidism. omega 3 FAs also restored levels of cerebellar phospho (p)-AKT, phospho-extracellular regulated kinase (p-ERK) and phospho-c-Jun N-terminal kinase (p-JNK), which were altered by hypothyroid insults, without interfering with the expression of TH responsive gene, myelin basic protein (mbp). Taken together, these results supplement an insight into the molecular mechanism of action of omega 3 FAs in developing brain that involves regulation of apoptotic signaling pathways under stress. (C) 2009 ISDN. Published by Elsevier Ltd. All rights reserved.”
“Bile GW4869 salts (BSs), in addition to their physiological role in the digestion of lipids in vertebrates, are also of significant importance in biomedical investigations. For predicting biological-pharmacological activity and physico-chemical properties of BSs it is important to develop such molecular
descriptors that adequately describe the structural characteristics of the steroid skeleton. The present study encompassed the following bile acids (BAs): cholic, chenodeoxycholic, deoxycholic, hyodeoxycholic, ursodeoxycholic, hyocholic, and ursocholic acid, as well as oxo derivatives of certain BAs. For all of them, Heuman hydrophobicity indices (HIBA) (RP-HPLC parameters) were determined, and a detailed conformational analysis of the steroid skeleton showed that HIBA has the discrimination power for BAs based on the size of the hydrophobic surface on the beta side and the lateral L7 and L12 sides of the steroid skeleton. Also, HIBA discerns the regiochemical characteristics of OH and oxo groups. Based on a survey of the structural factors of the steroid skeleton that influence the HIBA values of the tested BAs, we constructed a new molecular descriptor, CHIBA, with the characteristics of 2D and 3D topological descriptors.