ABSTRACT
Avaliou-se o efeito do GH in vitro sobre a expressão gênica do receptor LDL (RLDL) e da HMG-CoA redutase, bem como sobre a proliferação celular e acúmulo de lípides intracelulares em células mesangiais cultivadas em meio com soro deficiente de lipoproteínas (LPDS) durante 1, 2, 4 e 6 dias. A expressão coordenada entre o RLDL e a HMG-CoA redutase foi observada nas células mesangiais cultivadas em meio com LPDS. O GH aaumentou a proliferação das células mesangiais, dependente da sua concentração. A exposição prolongada ao GH induziu o aumento da expressão de RNAm do RLDL e da HMG-CoA redutase na células mesangiais, bem como o acúmulo de lípides neutros no citoplasma. Nos estudos in vivo...
Subject(s)
Animals , Cattle , Mice , Biochemistry/history , DNA , Gene Expression/genetics , Gene Expression/immunology , Glomerulosclerosis, Focal Segmental , In Vitro Techniques , Nephrology , Receptors, LDL , RNA , Cell Culture Techniques , Clinical Laboratory Techniques , Culture Media , Mice , Polymerase Chain Reaction , Receptors, Lipoprotein/administration & dosage , Receptors, Lipoprotein/analysis , SpectrophotometryABSTRACT
Low density lipoprotein (LDL) has been proposed as a drug targeting vector in cancer chemotherapy, however, research has been limited due to the necessity to isolate material from plasma. In this study, the physicochemical properties of synthetic lipid microemulsions containing an amphiphatic version of the apoprotein B receptor binding sequence have been examined. The effect of peptide sequence length, lipid anchor type and location along with microemulsion lipid composition were investigated via changes in particle size and zeta potential. Size increases were related to the amphiphatic peptides lipophilic portion and too a lesser extent by amino acid sequence length. Two lipophilic anchors, retinoic acid and cholesterol, produced large size increases whilst a single anchor (retinoic acid) did not affect size. The amphiphatic peptide reversed measured zeta potential from negative to positive values in a concentration dependent manner. This was related to peptide structure and could be effected by changes in pH, indicating that the peptide was surface located and responsive to the external environment. Alteration of microemulsion lipid composition also affected physicochemical properties but to a lesser degree than changes in the amphiphatic peptide. These novel systems may represent a useful synthetic alternative to native LDL for a variety of applications.