Dermal fibroblasts in Hutchinson-Gilford progeria syndrome with the lamin A G608G mutation have dysmorphic nuclei and are hypersensitive to heat stress

Background  

Hutchinson-Gilford progeria syndrome (HGPS, OMIM 176670) is a rare sporadic disorder with an incidence of approximately 1 per 8 million live births. The phenotypic appearance consists of short stature, sculptured nose, alopecia, prominent scalp veins, small face, loss of subcutaneous fat, faint mid-facial cyanosis, and dystrophic nails. HGPS is caused by mutations in LMNA, the gene that encodes nuclear lamins A and C. The most common mutation in subjects with HGPS is a de novo single-base pair substitution, G608G (GGC>GGT), within exon 11 of LMNA. This creates an abnormal splice donor site, leading to expression of a truncated protein.     

Invasive growth and topoisomerase-switch induced by tumorous extracellular matrix in osteosarcoma cell culture

Osteosarcoma cells are capable of extracellular matrix (ECM) synthesis. The ability of ECM to trigger the proliferation of a novel osteosarcoma cell line (OSCORT) was tested in this study in relation to a known tumor ECM, isolated from Engelbreth-Holm-Swarm (EHS) sarcoma (EHS-ECM). OSCORT was grown in monolayer, in EHS-ECM and in ECM deposited by the cells (OSCORT-ECM). Both EHS-ECM and OSCORT-ECM increased the proliferation and migration of OSCORT cells. Among the ECM biopolymers, heparan sulfate proteoglycan (HSPG) and fibronectin enhanced invasive growth, collagen type IV reduced it, while laminin had no effect. Among the ECM components HSPG and collagen IV increased both the synthesis and activation of collagenase type IV, and all the ECM components substantially increased beta1 integrin levels in the cells. The majority of ECM biopolymers decreased the level of topoisomerase I (except laminin) and elevated topoisomerase II (except fibronectin) in OSCORT. The switch in the ratio between the activities of topoisomerases I and II was mainly due to HSPG. The HSPG synthesized by OSCORT cells is described as agrin, which is a novel finding. The present study showed that HSPG (agrin) showed the most remarkable stimulatory action on the growth and migration of OSCORT cells. HSPG-induced topoisomerase II-induction deserves further experimentation, to discover its relevance to tumor progression.     

Novel stable analogues of the neurotensin C-terminal hexapeptide containing unnatural amino acids

Amino Acids - Neurotensin (NT) (pGlu–Leu–Tyr–Glu–Asn–Lys–Pro–Arg–Arg–Pro–Tyr–Ile–Leu) exerts a dual function as a...