Caroline Oliveira | Universidade Federal do Rio de Janeiro (UFRJ) (original) (raw)

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Papers by Caroline Oliveira

Journal of Cellular Physiology, 1990

In vitro studies of angiogenic phenomenon have been limited due to nonavailability of a simple an... more In vitro studies of angiogenic phenomenon have been limited due to nonavailability of a simple and biologically relevant model of the capillary wall. Recent development of a capillary endothelial cell line from the vascular bed of bovine adrenal medulla made us to study the effect of heparin, thrombin, thyroxine, glucagon, insulin, and phorbol myristate acetate (PMA) on the proliferative and metabolic activities such as glycosylation of asparagine-linked glycoproteins of these cells in culture. Out of six different agents studied here, only heparin, thrombin, and thyroxine reduced the doubling time of these cells by 24 hr with no observed morphological abnormality. Glucagon, showed marginal reduction in the cell doubling time. By contrast, insulin and PMA enhanced the doubling time. Insulin treatment though induced the S phase of cell cycle but it blocked the cells entry into the G2 + M phase. PMA arrested the cells in Go/G1 phase. The cellular response to protein N-glycosylation is increased in the presence of thyroxine, insulin, and thrombin and the effect is dose dependent. Further analysis on SDS-PAGE indicated that glycosylation of 80–120 kDa and 43 kDa glycoprotein species are enhanced when these cells are treated with insulin and thrombin. Glycopeptide generated from these glycoproteins suggested that they all carry “high mannose” and “complex” type oligosaccharide chains attached to their protein core.

Glycoconjugate Journal, 2006

During tumor growth and invasion, the endothelial cells from a relatively quiescent endothelium s... more During tumor growth and invasion, the endothelial cells from a relatively quiescent endothelium start proliferating. The exact mechanism of switching to a new angiogenic phenotype is currently unknown. We have examined the role of intracellular cAMP in this process. When a non-transformed capillary endothelial cell line was treated with 2 mM 8Br-cAMP, cell proliferation was enhanced by ∼70%. Cellular morphology indicated enhanced mitosis after 32–40 h with almost one-half of the cell population in the S phase. Bcl-2 expression and caspase-3, -8, and -9 activity remained unaffected. A significant increase in the Glc3Man9GlcNAc2-PP-Dol biosynthesis and turnover, Factor VIIIC N-glycosylation, and cell surface expression of N-glycans was observed in cells treated with 8Br-cAMP. Dol-P-Man synthase activity in the endoplasmic reticulum membranes also increased. A 1.4–1.6-fold increase in HSP-70 and HSP-90 expression was also observed in 8Br-cAMP treated cells. On the other hand, the expression of GRP-78/Bip was 2.3-fold higher compared to that of GRP-94 in control cells, but after 8Br-cAMP treatment for 32 h, it was reduced by 3-fold. GRP-78/Bip expression in untreated cells was 1.2–1.5-fold higher when compared with HSP-70 and HSP-90, whereas that of the GRP-94 was 1.5–1.8-fold lower. After 8Br-cAMP treatment, GRP-78/Bip expression was reduced 4.5–4.8-fold, but the GRP-94 was reduced by 1.5–1.6-fold only. Upon comparison, a 2.9-fold down-regulation of GRP-78/Bip was observed compared to GRP-94. We, therefore, conclude that a high level of Glc3Man9GlcNAc2-PP-Dol, resulting from 8Br-cAMP stimulation up-regulated HSP-70 expression and down-regulated that of the GRP-78/Bip, maintained adequate protein folding, and reduced endoplasmic reticulum stress. As a result capillary endothelial cell proliferation was induced.

Glycoconjugate Journal, 2003

Endothelial cells line blood vessels, and their proliferation during neovascularization (i.e., an... more Endothelial cells line blood vessels, and their proliferation during neovascularization (i.e., angiogenesis) is essential for a normal growth and development as well as for tumor progression and metastasis. Mechanistic details indicated that down-regulation of Glc3Man9GlcNAc2-PP-Dol level reduced angiogenesis and induced apoptosis in capillary endothelial cells (Martínez JA, Torres-Negrón I, Amigó LA, Banerjee DK, Cellular and Molec Biochem 45, 137–152 (1999)). Unlike in any other insulin-responsive cells, insulin reduced capillary endothelial cell proliferation by increasing the cell doubling time. But, when analyzed, the rate of lipid-linked oligosaccharide-PP-Dol (LLO) synthesis as well as its turnover (i.e., t1/2) were increased in insulin treated cells. No major differences in their molecular size were observed. This corroborated with an enhanced glycosylation of Factor VIIIC, an N-linked glycoprotein (essential cofactor of the blood coagulation cascade) and a marker for the capillary endothelial cell. Increased LLO synthesis was independent of elevating either Dol-P level or Man-P-Dol synthase gene (dpm) transcription. Insulin however, enhanced 2-deoxy-glucose transport across the endothelial cell plasma membrane and caused increased secretion of Factor VIIIC, thus, supporting the existence of additional LLO pool(s), and arguing favorably that growth retardation of capillary endothelial cells by insulin turned a highly proliferative cell into a highly secretory cell. Published in 2004.

Factor VIII is a large, 2,332-residue plasma glycoprotein that acts as a regulatory cofactor in t... more Factor VIII is a large, 2,332-residue plasma glycoprotein that acts as a regulatory cofactor in the process of blood coagulation [1–3]. It binds to activated factor IX (factor IXa) in the presence of calcium and negatively charged phospholipids at the surface of activated platelets to form a membrane-associated, proteolytically active complex. Upon complex formation, the V max of factor IXa is increased by approximately 200,000-fold, promoting the rapid activation of its substrate, the serine protease factor X. The proteolytic conversion of factor X to its active form, factor Xa, is a central control point in the coagulation cascade, leading to activation of thrombin, formation of a fibrin mesh, and establishment of a stable blood clot. The binding of factor VIIIc and other activated proteins to these membrane surfaces allows for localization of the procoagulation process to sites of vascular damage.

Anais Brasileiros De Dermatologia, 2008

Tungiasis is an ectoparasitic infection caused by the penetration of the sand flea Tunga penetran... more Tungiasis is an ectoparasitic infection caused by the penetration of the sand flea Tunga penetrans into the skin of the host. Flea infestation is associated with poverty and occurs in resource-poor communities in South and Central America, the Caribbean and Sub-Saharan Africa. In Brazil, it is widespread in urban squatter settlements, villages in the rural hinterland and in traditional fishing communities along the coast. Standard therapy for tungiasis consists of removing the embedded flea with a sterile needle, and using an antibiotic agent in case of secondary infection. At present, there is no drug in the market with satisfactory clinical efficacy. We describe a case of generalized Tunga penetrans infestation that was treated with oral ivermectin.

Cotidiano dos serviços: trabalhadores, usuários e familiares na produção do cuidado.

Journal of Cellular Physiology, 1990

In vitro studies of angiogenic phenomenon have been limited due to nonavailability of a simple an... more In vitro studies of angiogenic phenomenon have been limited due to nonavailability of a simple and biologically relevant model of the capillary wall. Recent development of a capillary endothelial cell line from the vascular bed of bovine adrenal medulla made us to study the effect of heparin, thrombin, thyroxine, glucagon, insulin, and phorbol myristate acetate (PMA) on the proliferative and metabolic activities such as glycosylation of asparagine-linked glycoproteins of these cells in culture. Out of six different agents studied here, only heparin, thrombin, and thyroxine reduced the doubling time of these cells by 24 hr with no observed morphological abnormality. Glucagon, showed marginal reduction in the cell doubling time. By contrast, insulin and PMA enhanced the doubling time. Insulin treatment though induced the S phase of cell cycle but it blocked the cells entry into the G2 + M phase. PMA arrested the cells in Go/G1 phase. The cellular response to protein N-glycosylation is increased in the presence of thyroxine, insulin, and thrombin and the effect is dose dependent. Further analysis on SDS-PAGE indicated that glycosylation of 80–120 kDa and 43 kDa glycoprotein species are enhanced when these cells are treated with insulin and thrombin. Glycopeptide generated from these glycoproteins suggested that they all carry “high mannose” and “complex” type oligosaccharide chains attached to their protein core.

Glycoconjugate Journal, 2006

During tumor growth and invasion, the endothelial cells from a relatively quiescent endothelium s... more During tumor growth and invasion, the endothelial cells from a relatively quiescent endothelium start proliferating. The exact mechanism of switching to a new angiogenic phenotype is currently unknown. We have examined the role of intracellular cAMP in this process. When a non-transformed capillary endothelial cell line was treated with 2 mM 8Br-cAMP, cell proliferation was enhanced by ∼70%. Cellular morphology indicated enhanced mitosis after 32–40 h with almost one-half of the cell population in the S phase. Bcl-2 expression and caspase-3, -8, and -9 activity remained unaffected. A significant increase in the Glc3Man9GlcNAc2-PP-Dol biosynthesis and turnover, Factor VIIIC N-glycosylation, and cell surface expression of N-glycans was observed in cells treated with 8Br-cAMP. Dol-P-Man synthase activity in the endoplasmic reticulum membranes also increased. A 1.4–1.6-fold increase in HSP-70 and HSP-90 expression was also observed in 8Br-cAMP treated cells. On the other hand, the expression of GRP-78/Bip was 2.3-fold higher compared to that of GRP-94 in control cells, but after 8Br-cAMP treatment for 32 h, it was reduced by 3-fold. GRP-78/Bip expression in untreated cells was 1.2–1.5-fold higher when compared with HSP-70 and HSP-90, whereas that of the GRP-94 was 1.5–1.8-fold lower. After 8Br-cAMP treatment, GRP-78/Bip expression was reduced 4.5–4.8-fold, but the GRP-94 was reduced by 1.5–1.6-fold only. Upon comparison, a 2.9-fold down-regulation of GRP-78/Bip was observed compared to GRP-94. We, therefore, conclude that a high level of Glc3Man9GlcNAc2-PP-Dol, resulting from 8Br-cAMP stimulation up-regulated HSP-70 expression and down-regulated that of the GRP-78/Bip, maintained adequate protein folding, and reduced endoplasmic reticulum stress. As a result capillary endothelial cell proliferation was induced.

Glycoconjugate Journal, 2003

Endothelial cells line blood vessels, and their proliferation during neovascularization (i.e., an... more Endothelial cells line blood vessels, and their proliferation during neovascularization (i.e., angiogenesis) is essential for a normal growth and development as well as for tumor progression and metastasis. Mechanistic details indicated that down-regulation of Glc3Man9GlcNAc2-PP-Dol level reduced angiogenesis and induced apoptosis in capillary endothelial cells (Martínez JA, Torres-Negrón I, Amigó LA, Banerjee DK, Cellular and Molec Biochem 45, 137–152 (1999)). Unlike in any other insulin-responsive cells, insulin reduced capillary endothelial cell proliferation by increasing the cell doubling time. But, when analyzed, the rate of lipid-linked oligosaccharide-PP-Dol (LLO) synthesis as well as its turnover (i.e., t1/2) were increased in insulin treated cells. No major differences in their molecular size were observed. This corroborated with an enhanced glycosylation of Factor VIIIC, an N-linked glycoprotein (essential cofactor of the blood coagulation cascade) and a marker for the capillary endothelial cell. Increased LLO synthesis was independent of elevating either Dol-P level or Man-P-Dol synthase gene (dpm) transcription. Insulin however, enhanced 2-deoxy-glucose transport across the endothelial cell plasma membrane and caused increased secretion of Factor VIIIC, thus, supporting the existence of additional LLO pool(s), and arguing favorably that growth retardation of capillary endothelial cells by insulin turned a highly proliferative cell into a highly secretory cell. Published in 2004.

Factor VIII is a large, 2,332-residue plasma glycoprotein that acts as a regulatory cofactor in t... more Factor VIII is a large, 2,332-residue plasma glycoprotein that acts as a regulatory cofactor in the process of blood coagulation [1–3]. It binds to activated factor IX (factor IXa) in the presence of calcium and negatively charged phospholipids at the surface of activated platelets to form a membrane-associated, proteolytically active complex. Upon complex formation, the V max of factor IXa is increased by approximately 200,000-fold, promoting the rapid activation of its substrate, the serine protease factor X. The proteolytic conversion of factor X to its active form, factor Xa, is a central control point in the coagulation cascade, leading to activation of thrombin, formation of a fibrin mesh, and establishment of a stable blood clot. The binding of factor VIIIc and other activated proteins to these membrane surfaces allows for localization of the procoagulation process to sites of vascular damage.

Anais Brasileiros De Dermatologia, 2008

Tungiasis is an ectoparasitic infection caused by the penetration of the sand flea Tunga penetran... more Tungiasis is an ectoparasitic infection caused by the penetration of the sand flea Tunga penetrans into the skin of the host. Flea infestation is associated with poverty and occurs in resource-poor communities in South and Central America, the Caribbean and Sub-Saharan Africa. In Brazil, it is widespread in urban squatter settlements, villages in the rural hinterland and in traditional fishing communities along the coast. Standard therapy for tungiasis consists of removing the embedded flea with a sterile needle, and using an antibiotic agent in case of secondary infection. At present, there is no drug in the market with satisfactory clinical efficacy. We describe a case of generalized Tunga penetrans infestation that was treated with oral ivermectin.

Cotidiano dos serviços: trabalhadores, usuários e familiares na produção do cuidado.