LUIZ FERNANDO ONUCHIC
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/29 - Laboratório de Nefrologia Celular, Genética e Molecular, Hospital das Clínicas, Faculdade de Medicina - Líder
9 resultados
Resultados de Busca
Agora exibindo 1 - 9 de 9
conferenceObject Integrated Analyses of Gene, Protein and miRNA Expression in Bladder Cancer Patients Reveals a Link Between mTOR and Differentiation(2018) SCHULTZ, Luciana; CAMILLO, Claudia; SCHULTZ, Andre; PUGA, Renato; CASTRO, Isac de; CHANDRASHEKAR, Darshan S.; SPAGNUL, Samuel J.; CUNHA, Isabela W. da; VARAMBALLY, Sooryanarayana; NETTO, George J.; ONUCHIC, Luiz F.; SOARES, FernandoconferenceObject Dendrogram Analyses of Relative Expression Between Bladder Cancers and Controls Identify PTEN-HIF1 alpha Association as an Alteration Characteristic of Malignancy(2015) SCHULTZ, Luciana; COUTINHO-CAMILLO, Claudia; CASTRO, Isac; DAMM, Gilcy; SPAGNUL, Samuel; CUNHA, Isabela; ONUCHIC, Luiz; SOARES, Fernando- Disruption of polycystin-1 cleavage leads to cardiac metabolic rewiring in mice(2022) AMARAL, Andressa G.; SILVA, Camille C. C. da; SERNA, Julian D. C.; HONORATO-SAMPAIO, Kinulpe; FREITAS, Jessica A.; DUARTE-NETO, Amaro N.; BLOISE, Antonio C.; CASSINA, Laura; YOSHINAGA, Marcos Y.; CHAVES-FILHO, Adriano B.; QIAN, Feng; MIYAMOTO, Sayuri; BOLETTA, Alessandra; BORDIN, Silvana; KOWALTOWSKI, Alicia J.; ONUCHIC, Luiz F.Cardiovascular manifestations account for marked morbi-mortality in autosomal dominant polycystic kidney disease (ADPKD). Pkd1- and Pkd2-deficient mice develop cardiac dysfunction, however the underlying mechanisms remain largely unclear. It is unknown whether impairment of polycystin-1 cleavage at the G-proteincoupled receptor proteolysis site, a significant ADPKD mutational mechanism, is involved in this process. We analyzed the impact of polycystin-1 cleavage on heart metabolism using Pkd1V/V mice, a model unable to cleave this protein and with early cardiac dysfunction. Pkd1V/V hearts showed lower levels of glucose and amino acids and higher lipid levels than wild-types, as well as downregulation of p-AMPK, p-ACC beta, CPT1B-Cpt1b, Ppara, Nppa and Acta1. These findings suggested decreased fatty acid beta-oxidation, which was confirmed by lower oxygen consumption by Pkd1V/V isolated mitochondria using palmitoyl-CoA. Pkd1V/V hearts also presented increased oxygen consumption in response to glucose, suggesting that alternative substrates may be used to generate energy. Pkd1V/V hearts displayed a higher density of decreased-size mitochondria, a finding associated with lower MFN1, Parkin and BNIP3 expression. These derangements were correlated with increased apoptosis and inflammation but not hypertrophy. Notably, Pkd1V/V neonate cardiomyocytes also displayed shifts in oxygen consumption and p-AMPK downregulation, suggesting that, at least partially, the metabolic alterations are not induced by kidney dysfunction. Our findings reveal that disruption of polycystin-1 cleavage leads to cardiac metabolic rewiring in mice, expanding the understanding of heart dysfunction associated with Pkd1 deficiency and likely with human ADPKD.
conferenceObject Low Immunoexpression of phosAKT Correlates With Upregulation of mTOR Pathway and HIFI a Gene Expression(2015) COUTINHO-CAMILLO, Claudia; SCHULTZ, Luciana; CASTRO, Isac; DAMM, Gilcy; CUNHA, Isabela; ONUCHIC, Luiz; SOARES, FernandoconferenceObject Dendrogram Analyses of Relative Expression Between Bladder Cancers and Controls Identify PTEN-HIF1 alpha Association as an Alteration Characteristic of Malignancy(2015) SCHULTZ, Luciana; COUTINHO-CAMILLO, Claudia; CASTRO, Isac; DAMM, Gilcy; SPAGNUL, Samuel; CUNHA, Isabela; ONUCHIC, Luiz; SOARES, FernandoconferenceObject Low Immunoexpression of phosAKT Correlates With Upregulation of mTOR Pathway and HIF1a Gene Expression(2015) COUTINHO-CAMILLO, Claudia; SCHULTZ, Luciana; CASTRO, Isac; DAMM, Gilcy; CUNHA, Isabela; ONUCHIC, Luiz; SOARES, FernandoconferenceObject Expression of Fibrocystin/Polyductin in Cholangiocarcinoma Cell Lines (OZ, Huh-28 and HuCCT-1)(2012) SERGI, C.; ONUCHIC, L.; ABUETABH, Y.; NAGAMORI, S.- Lipoprotein glomerulopathy associated with the Osaka/Kurashiki APOE variant: two cases identified in Latin America(2021) SILVEIRA-NETO, Joaquim Nelito Da; AHN, Guilherme Jinson de Oliveira; NEVES, Precil Diego Miranda de Menezes; BAPTISTA, Vinicius Augusto Ferreira; ARAUJO, Stanley de Almeida; WANDERLEY, David Campos; WATANABE, Andreia; WATANABE, Elieser Hitoshi; MURAI, Neide Missae; BERTOLLO, Eny Maria Goloni; VIEIRA-NETO, Osvaldo Merege; DANTAS, Marcio; ANTONIO, Sergio Ricardo de; COSTA, Roberto Silva; BAPTISTA, Maria Alice Sperto Ferreira; MOYSES-NETO, Miguel; ONUCHIC, Luiz FernandoBackground Lipoprotein glomerulopathy (LPG) is a rare autosomal dominant disease caused by mutations in APOE, the gene which encodes apolipoprotein E. LPG mainly affects Asian individuals, however occasional cases have also been described in Americans and Europeans. Herein we report two unrelated Brazilian patients with LPG in whom genetic analyses revealed the APOE-Osaka/Kurashiki variant. Case presentation - case 1 A 29-year-old Caucasian male sought medical attention with complaints of face swelling and foamy urine for the last 3 months. He denied a family history of kidney disease, consanguinity, or Asian ancestry. His tests showed proteinuria of 12.5 g/24 h, hematuria, serum creatinine 0.94 mg/dL, albumin 2.3 g/dl, total cholesterol 284 mg/dL, LDL 200 mg/dL, triglycerides 175 mg/dL, and negative screening for secondary causes of glomerulopathy. A kidney biopsy revealed intraluminal, laminated deposits of hyaline material in glomerular capillaries consistent with lipoprotein thrombi. These findings were confirmed by electron microscopy, establishing the diagnosis of LPG. His apolipoprotein E serum level was 72 mg/dL and genetic analysis revealed the APOE pathogenic variant c.527G > C, p.Arg176Pro in heterozygosis, known as the Osaka/Kurashiki mutation and positioned nearby the LDL receptor binding site. Case 2 A 34-year-old Caucasian man sought medical assessment for renal dysfunction and hypertension. He reported intermittent episodes of lower-limb edema for 3 years and a family history of kidney disease, but denied Asian ancestry. Laboratorial tests showed BUN 99 mg/dL, creatinine 10.7 mg/dL, total cholesterol 155 mg/dL, LDL 79 mg/dL, triglycerides 277 mg/dL, albumin 3.1 g/dL, proteinuria 2.7 g/24 h, and negative screening for secondary causes of glomerulopathy. His kidney biopsy was consistent with advanced chronic nephropathy secondary to LPG. A genetic analysis also revealed the Osaka/Kurashiki variant. He was transplanted a year ago, displaying no signs of disease relapse. Conclusion We report two unrelated cases of Brazilian patients with a diagnosis of lipoprotein glomerulopathy whose genetic assessment identified the APOE-Osaka/Kurashiki pathogenic variant, previously only described in eastern Asians. While this is the second report of LPG in Latin America, the identification of two unrelated cases by our medical team raises the possibility that LPG may be less rare in this part of the world than currently thought, and should definitely be considered when nephrotic syndrome is associated with suggestive kidney biopsy findings.
conferenceObject Integrated Analyses of Gene, Protein and miRNA Expression in Bladder Cancer Patients Reveals a Link Between mTOR and Differentiation(2018) SCHULTZ, Luciana; CAMILLO, Claudia; SCHULTZ, Andre; PUGA, Renato; CASTRO, Isac de; CHANDRASHEKAR, Darshan S.; SPAGNUL, Samuel J.; CUNHA, Isabela W. da; VARAMBALLY, Sooryanarayana; NETTO, George J.; ONUCHIC, Luiz F.; SOARES, Fernando