Identification of Novel Proteins Interacting with Proprotein Convertase Subtilisin/Kexin 9.

High levels of cholesterol, especially as low-density lipoprotein (LDL), are a well-known risk factor for atherosclerotic-related diseases. The key atherogenic property of LDL is its ability to form atherosclerotic plaque. Proprotein convertase subtilisin/kexin-9 (PCSK9) is an indirect regulator of plasma LDL levels by controlling the number of LDL receptor molecules expressed at the plasma membrane, especially in the liver. Herein, we performed a combination of affinity chromatography, mass spectrometry analysis and identification, and gene expression studies to identify proteins that interact with PCSK9. Through these studies, we identified three proteins, alpha-1-antitrypsin (A1AT), alpha-1-microglobulin/bikunin precursor (AMBP), and apolipoprotein H (APOH) expressed by C3A cells that interact with PCSK9. The expression levels of A1AT and APOH increased in cells treated with MITO+ medium, a condition previously shown to affect the function of PCSK9, as compared to treating with Regular (control) medium. However, AMBP expression did not change in response to the treatments. Additional studies are required to determine which of these proteins can modulate the expression/function of PCSK9. The identification of endogenous modulators of PCSK9's function could lead to the development of novel diagnostic tests or treatment options for patients suffering hypercholesterolemia in combination with other chronic metabolic diseases.

Caracterización clínica y severidad de los trastornos temporomandibulares en pacientes adultos / Clinical characterization and severity of temporomandibular disorders in adult patients

RESUMEN Fundamento: los trastornos temporomandibulares son afecciones en la articulación temporomandibular, musculatura masticatoria, estructuras asociadas y de forma general los trastornos relacionados con la función del sistema estomatognático. Objetivo: determinar la caracterización clínica y severidad de los trastornos temporomandibulares en pacientes adultos. Métodos: se realizó un estudio descriptivo trasversal en la consulta de Prótesis Estomatológica del municipio Nuevitas, provincia Camagüey, desde de enero a julio de 2018, de un universo de 133 pacientes diagnosticados con trastornos temporomandibulares, previo cálculo muestral se seleccionó una muestra no probabilística constituida por 77 pacientes. Resultados: predominó el sexo femenino y el grupo de edad entre 40-49 años. Se destacó como principal grado de disfunción la moderada. Se observó el estrés emocional, las interferencias oclusales y el bruxismo como factores de riesgo. Las principales manifestaciones clínicas encontradas en los pacientes examinados fueron los ruidos articulares en el 71,4 %. Conclusiones: la caracterización clínica y severidad de los trastornos temporomandibulares permitió conocer un predominio en el sexo femenino, durante la cuarta década de vida, con un grado de disfunción moderada, donde los principales factores de riesgo fueron el estrés emocional, interferencias oclusales y bruxismo. La mayoría de los pacientes presentaron ruidos articulares como principal manifestación clínica.

ABSTRACT Background: temporomandibular disorders are conditions in the Temporomandibular Joint, masticatory muscles, associated structures and disorders related to the function of the stomatognatic system. Objective: to determine the clinical characterization and severity of temporomandibular disorders in adult patients Methods: a cross-sectional descriptive study was carried out in the Dentistry Prosthesis consultation of the municipality of Nuevitas, Camagüey province, in the period from January to July 2018, from a universe of 133 patients diagnosed with temporomandibular disorders, a non-probabilistic sample was selected constituted by 77 patients, previous sample calculation. Results: the female sex predominated and the age group between 40-49 years. It was highlighted as the main degree of dysfunction according to the moderate. Observed emotional stress, occlusal interferences, and bruxism as risk factors was observed. The main clinical manifestations in the patients examined were joint noises in 71.4 %. Conclusions: the clinical characterization and severity of the temporomandibular disorders allowed to know a predominance in the female sex, during the fourth decade of life, with a moderate degree of dysfunction, where the main risk factors were emotional stress, occlusal interferences and bruxism. The majority of patients presented main clinical manifestation.

Identification of Proteins Interacting with PCSK9 Using a Protoarray Human Protein Microarray.

Proprotein convertase subtilisin-kexin 9 (PCSK9) appears to be involved in multiple processes. A ProtoArray Human Protein Microarray was used to identify proteins interacting with biotinylated PCSK9. Fifteen novel proteins interacting with PCSK9 were identified using this technique. Only two of these proteins, sterol carrier protein 2 and hepatoma-derived growth factor, related protein 3, have known functions. The identification of proteins that could affect the expression/function of PCSK9 is of great interest due to potential implications in personalized medicine for hypercholesterolemic patients.

Preparation of a Functional Rat LDL Receptor Minigene.

The majority of the low-density lipoprotein (LDL) receptors present in the body are expressed in the liver. Therefore, plasma LDL levels significantly correlate with changes in the activity of the hepatic LDL receptor. Based on this, there is a need to understand the regulatory mechanisms that control the hepatic expression of the low-density lipoprotein (LDL) receptor. Herein, we have prepared a functional rat LDL receptor minigene construct that can produce mRNA after splicing. Sequence analysis suggests that this construct has the potential to code for a truncated version of LDL receptor protein. This minigene could be used as a research tool to identify small molecules, natural products, and regulators of the LDL receptor gene that could be developed into LDL receptor-specific activators for therapeutic use.

Atorvastatin and lovastatin, but not pravastatin, increased cellular complex formation between PCSK9 and the LDL receptor in human hepatocyte-like C3A cells.

Statins are the first-line treatment for hypercholesterolemic patients. Herein, the effects of three statins on complex formation between proprotein convertase subtilisin-kexin 9 (PCSK9) and the low density lipoprotein receptor (LDLR), a critical step for the PCSK9-dependent degradation of LDLR in the lysosome, were examined. Human hepatocyte-like C3A cells grown in control (containing 10% fetal bovine serum) or MITO+ (supplemented with BD™ MITO + serum extender) medium were also treated with atorvastatin (Atorv), lovastatin (Lov), or pravastatin (Prav) for 24 h. RNA and protein expression studies and determinations of PCSK9/LDLR complex formation were performed. As expected, the statins increased the expression of PCSK9 and LDLR independently of the medium employed. Interestingly, Atov and Lov caused increases in PCSK9/LDLR complex formation, whereas Prav decreased complex formation when compared to cells treated without drugs. These results may explain why Prav works better for statin intolerant patients than other statins such as Atorv and Lov.

Hypercholesterolemia: The role of PCSK9.

Heart disease ends the life of more people than any other disease in the United States. High levels of low density lipoprotein (LDL)-cholesterol cause heart diseases by increasing the formation of atherosclerotic plaques. Proprotein convertase subtilisin/kexin-9 (PCSK9) indirectly regulates plasma LDL levels by controlling the LDL receptor expression at the plasma membrane. PCSK9 also appears to modulate glucose intolerance, insulin resistance, abdominal obesity, inflammation, and hypertension. The magnitude of PCSK9's involvement in the onset of these metabolic abnormalities appears to be associated with age, sex, and ethnic background. Another regulator, the inducible degrader of the LDL receptor (IDOL), works by enhancing the ubiquitination of the LDL receptor. Herein, we will review the functions and regulatory mechanisms of PCSK9. The effects of PCSK9 on the LDL receptor, the relationship of this convertase with IDOL, and treatments currently available against hypercholesterolemia are also discussed.

Algunas causales relacionadas con caídas en el hogar del adulto mayor / Some causes related to falls in the home of the elderly

Introducción: dentro de los grandes síndromes invalidantes en el adulto mayor se encuentran las caídas, las cuales son causa de atención y de estudio por el aumento de casos reportados. Objetivo: identificar algunas causales responsables en las caídas en el adulto mayor en el hogar. Métodos: se realizaron encuestas con el consentimiento informado, la población estuvo conformada por 1 903 adultos mayores de ambos sexos asistidos en consulta de fisiatría, y cuya muestra intencional lo conformaron 632 pacientes caídos en el hogar, constituyendo el 33,2 por ciento. Resultados: hubo un predominio de caídas en el sexo femenino, por otra parte las fracturas de cadera fue la secuela que más predominó y sobre todo en el sexo femenino. Dentro de los factores extrínsecos, las caídas en baños peligrosos fueron las causantes más frecuentes y más del 50 por ciento en los pacientes que no practican ninguna actividad física. Conclusiones: el trabajo realizado permitió identificar causales, constatar la atención del Sistema de Salud del área y desarrollar acciones para una mejor calidad de vida en el adulto mayor (AU)

Introduction: low underweight when being born is the most important index to determine the possibilities of the newly born one to survive and to have a growth and normal development, one of the main current obstetric problems constitutes because it is related with more than 75 percent of the perinatal morbimortality Objective: determiner the incidence and the main factors of risk associated to the first floor weight in San Antonio of the Bathrooms Method: he/she was carried out a retrospective descriptive observational study in the newly born ones with underweight when being born of the municipality of San Antonio of the Bathrooms, county Artemisia Cuba, the period of January to December of the 2013.El universe was constituted by 564 newly born alive and the sample for 29 with underweight when being born, it was identified prenatal factors that could constitute possible causes of the first floor weight. Results: the incidence of the first floor weight when being born in the year 2013 in San Antonio of the Bathrooms was of 5,9.El 58,62 percent of the low pesos 37 of gestation they were born before the week. The most represented maternal age went from 20 to 34 years with 62, 06 percent. The vaginal sepsis was present in 51, 80 percent of the mothers with newly born under weight. Conclusions: the prematurity was the most frequent cause of newly born under weight when being born, the extreme ages of the reproductive life didn't constitute cause of underweight when being born, the vaginal sepsis and the arterial hypertension are outstanding factors of risk in the mothers with children under weight (AU)

Algunas causales relacionadas con caídas en el hogar del adulto mayor / Some causes related to falls in the home of the elderly

Introducción: dentro de los grandes síndromes invalidantes en el adulto mayor se encuentran las caídas, las cuales son causa de atención y de estudio por el aumento de casos reportados. Objetivo: identificar algunas causales responsables en las caídas en el adulto mayor en el hogar. Métodos: se realizaron encuestas con el consentimiento informado, la población estuvo conformada por 1 903 adultos mayores de ambos sexos asistidos en consulta de fisiatría, y cuya muestra intencional lo conformaron 632 pacientes caídos en el hogar, constituyendo el 33,2 %. Resultados: hubo un predominio de caídas en el sexo femenino, por otra parte las fracturas de cadera fue la secuela que más predominó y sobre todo en el sexo femenino. Dentro de los factores extrínsecos, las caídas en baños peligrosos fueron las causantes más frecuentes y más del 50 % en los pacientes que no practican ninguna actividad física. Conclusiones: el trabajo realizado permitió identificar causales, constatar la atención del Sistema de Salud del área y desarrollar acciones para una mejor calidad de vida en el adulto mayor.

Introduction: low underweight when being born is the most important index to determine the possibilities of the newly born one to survive and to have a growth and normal development, one of the main current obstetric problems constitutes because it is related with more than 75 % of the perinatal morbimortality Objective: determiner the incidence and the main factors of risk associated to the first floor weight in San Antonio of the Bathrooms Method: he/she was carried out a retrospective descriptive observational study in the newly born ones with underweight when being born of the municipality of San Antonio of the Bathrooms, county Artemisia Cuba, the period of January to December of the 2013.El universe was constituted by 564 newly born alive and the sample for 29 with underweight when being born, it was identified prenatal factors that could constitute possible causes of the first floor weight. Results: the incidence of the first floor weight when being born in the year 2013 in San Antonio of the Bathrooms was of 5,9.El 58,62 % of the low pesos 37 of gestation they were born before the week. The most represented maternal age went from 20 to 34 years with 62, 06 %. The vaginal sepsis was present in 51, 80 % of the mothers with newly born under weight. Conclusions: the prematurity was the most frequent cause of newly born under weight when being born, the extreme ages of the reproductive life didn't constitute cause of underweight when being born, the vaginal sepsis and the arterial hypertension are outstanding factors of risk in the mothers with children under weight.

Distribution of the LDL receptor within clathrin-coated pits and caveolae in rat and human liver.

Several findings suggest that the low-density lipoprotein (LDL) receptor may internalize different lipoprotein particles via diverse pathways. Using a combination of discontinuous sucrose gradients and Triton solubilization studies, we demonstrated that the LDL receptor could be located simultaneously in clathrin-coated pits and caveolae in rat and human liver and in human hepatocyte-like C3A cells. Treatment with the cholesterol biosynthesis inhibitor, zaragozic acid A, shifted the distribution of the LDL receptor to clathrin containing fractions, whereas treatment with cholesterol or LDL shifted the receptor distribution towards caveolin-1 containing fractions. The LDL-dependent shift of the LDL receptor to caveolae coincided with a reduction in internalization of Bodipy-LDL. Redistribution within plasma membrane microdomains in response to specific treatments resulting in changes in LDL receptor function represents a novel paradigm that could be exploited in the development of a new class of therapeutic drugs.

Having excess levels of PCSK9 is not sufficient to induce complex formation between PCSK9 and the LDL receptor.

Proprotein convertase subtilisin/kexin-9 (PCSK9) acts mainly by forming complexes with the LDL receptor at the cell surface, which are then degraded in the lysosome. Studies were performed to determine whether excess levels of PCSK9 was sufficient to induce PCSK9/LDL receptor complex formation in human hepatocyte-like C3A cells. It was demonstrated using ELISA that instead of considering the overall levels of PCSK9 protein that is produced in response to certain treatment, what is critical is how much PCSK9 is actually capable of forming complexes. Despite the high levels, most of the PCSK9 produced as a result of incubating cells with a medium supplemented with BD™ MITO+ serum extender (MITO+ medium) appeared to be inhibited by a secreted factor. Having lower levels of PCSK9/LDL receptor complexes did not prevent an increase in the degradation rate of LDL receptors in MITO+ medium as compared to fetal bovine serum (FBS) containing medium (Regular medium), an effect that did not correlate with an increase in protein levels of the inducible degrader of LDL receptors (IDOL), as demonstrated using Western blotting analysis. Additional studies are required to determine the exact mechanism(s) for the degradation of the LDL receptor and/or to identify the secreted inhibitor of PCSK9.

Using in vivo electroporation to identify hepatic LDL receptor promoter elements and transcription factors mediating activation of transcription by T3.

The technique of in vivo electroporation was adapted to investigate the promoter elements and transcription factors mediating the rapid induction of hepatic LDL receptor expression in response to thyroid hormone. Direct comparisons between wild type and mutant promoter constructs were made within the same animal. It was demonstrated that both TREs at bp - 612 and - 156 were required for the l-triiodothyronine (T3) response. ChIP analysis showed that binding of TRß1 to the - 612 and - 156 TREs was markedly stimulated by T3in vivo. Introduction of siRNAs against TRß1/RXRα with LDL receptor promoter-luciferase construct by in vivo electroporation demonstrated that these transcription factors play the major physiological role in the activation of hepatic LDL receptor transcription. The findings agree with those made by transfecting H4IIE cells in vitro thus validating this technique for in vivo studies of mechanisms of transcriptional regulation. The findings reported herein also indicated, for the first time, that PPARα and USF-2 were required for maximum transcriptional activation of the LDL receptor in response to T3 treatment.

Primer reporte familiar de Inermicapsifer magadascariensis (cubensis) / First family report of Inermicapsifer magadascariensis (cubensis)

Se informa por primera vez la presencia de parasitismo intestinal por Inermicapsifer madagascariensis en una familia del municipio Santa Cruz Sur de la provincia de Camagüey. El brote se detectó a partir de investigaciones realizadas a una menor de 18 meses de edad remitida a consulta de parasitología por presentar inapetencia, pérdida de peso, diarreas semipastosas y líquidas, anorexia y dolor abdominal. Los síntomas antes mencionados se presentaron también en el resto de la familia (mamá y abuelo). El diagnóstico se confirmó al enviar las muestras de heces fecales al laboratorio provincial de parasitología, donde se constató la presencia de los proglótides del parásito en todos los pacientes. Las personas afectadas recibieron tratamiento con prazicuantel a dosis establecida, luego de indicarles otros complementarios. La presencia de perros y roedores se comprobó a través de la encuesta epidemiológica. No se han reportado brotes similares en nuestro país según la literatura consultada(AU)

It is informed the presence of intestinal parasitism for the first time by Inermicapsifer madagascariensis in a family from Santa Cruz del Sur municipality of Camagüey province. The outbreak was detected starting from investigations carried out to a smaller child of 18 months remitted to the parasitology consultation to present inappetence, loss of weight, watery and semiclammy diarrheas, anorexy and abdominal pain. The mentioned symptoms also showed up in the rest of the family (mother and grandfather). The diagnosis was confirmed when sending the samples of feces to the provincial laboratory of parasitology, where the presence of the proglottids of the parasite was verified in all the patients. Affected people received treatment with prazicuantel to established dose, after indicating them other complementaries. The presence of dogs and rodents were proven through the epidemic survey. Similar outbreaks have not been reported in our country according to the reviewed literature(AU)

Primer reporte familiar de Inermicapsifer magadascariensis (cubensis) / First family report of Inermicapsifer magadascariensis (cubensis)

Se informa por primera vez la presencia de parasitismo intestinal por Inermicapsifer madagascariensis en una familia del municipio Santa Cruz Sur de la provincia de Camagüey. El brote se detectó a partir de investigaciones realizadas a una menor de 18 meses de edad remitida a consulta de parasitología por presentar inapetencia, pérdida de peso, diarreas semipastosas y líquidas, anorexia y dolor abdominal. Los síntomas antes mencionados se presentaron también en el resto de la familia (mamá y abuelo). El diagnóstico se confirmó al enviar las muestras de heces fecales al laboratorio provincial de parasitología, donde se constató la presencia de los proglótides del parásito en todos los pacientes. Las personas afectadas recibieron tratamiento con prazicuantel a dosis establecida, luego de indicarles otros complementarios. La presencia de perros y roedores se comprobó a través de la encuesta epidemiológica. No se han reportado brotes similares en nuestro país según la literatura consultada

It is informed the presence of intestinal parasitism for the first time by Inermicapsifer madagascariensis in a family from Santa Cruz del Sur municipality of Camagüey province. The outbreak was detected starting from investigations carried out to a smaller child of 18 months remitted to the parasitology consultation to present inappetence, loss of weight, watery and semiclammy diarrheas, anorexy and abdominal pain. The mentioned symptoms also showed up in the rest of the family (mother and grandfather). The diagnosis was confirmed when sending the samples of feces to the provincial laboratory of parasitology, where the presence of the proglottids of the parasite was verified in all the patients. Affected people received treatment with prazicuantel to established dose, after indicating them other complementaries. The presence of dogs and rodents were proven through the epidemic survey. Similar outbreaks have not been reported in our country according to the reviewed literature

Tumor-induced upregulation of Twist, Snail, and Slug represses the activity of the human VE-cadherin promoter.

Endothelial integrity is dependent on intracellular adherens junctions formed by complexes of vascular endothelial (VE)-cadherin and catenins. We have previously demonstrated that exposing endothelial cells (EC) to breast cancer cell-conditioned media (CM) for 24h results in a reduction in VE-cadherin protein and mRNA levels. Herein, we examined the mechanism(s) involved in the downregulation of VE-cadherin by CM. Human dermal microvascular EC exposed to CM showed a downregulation in VE-cadherin promoter activity and upregulation of Twist, Slug, and Snail expression. Reporter gene analysis demonstrated a direct repression of the VE-cadherin promoter by Slug, Snail, and Twist expression plasmids. At least two E-box motifs appear to be involved in this regulatory process as shown by electrophoretic mobility shift assays. These results suggest that factors released by breast cancer cells are able to upregulate Twist, Slug, and Snail expression in EC, which in turn downregulate the activity of the VE-cadherin promoter.

Estrongiloidosis crónica: reporte de un caso / Chronic strongyloidosis: a case report

Se describe el caso de una adolescente de 15 años remitida a la consulta de parasitología del Policlínico de Especialidades Pediátricas de Camagüey, por presentar una eosinofilia marcada y lesiones purpúricas en cara y tórax, acompañadas de fiebre y vómitos con estrías de sangre. Se le indicó copa cónica en heces fecales y se observaron larvas de Strongyloides stercoralis, la biopsia de piel arrojó edema del dermis papilar y focos hemorrágicos, lesiones que se pueden presentar en pacientes con infección por esta parasitosis. En la encuesta epidemiológica se comprobó que la paciente acostumbraba a andar sin calzado con frecuencia y se constataron las malas condiciones higiénico-sanitarias en el hogar. Este caso constituye el primer reporte de estrongiloidosis crónica en la provincia(AU)

The case of a 15 year-old adolescent remitted to the parasitology consultation at Pediatric Specialties Polyclinic of Camagüey is described, by presenting a marked eosinophilia and purpuric lesions in face and thorax, accompanied by fever and vomits with striae of blood. It was indicated conical cup in feces and Strongyloides stercoralis larvae were observed, the skin biopsy showed edema of the papillary dermis and hemorrhagic focuses, lesions that can show up in patients with infection for this parasitosis. In the epidemiological survey was proved that the patient frequently used to walk without having no shoes and bad hygienic-sanitary conditions at home were verified. This case constitutes the first chronic strongyloidosis report in the province(AU)

Estrongiloidosis crónica: reporte de un caso / Chronic strongyloidosis: a case report

Se describe el caso de una adolescente de 15 años remitida a la consulta de parasitología del Policlínico de Especialidades Pediátricas de Camagüey, por presentar una eosinofilia marcada y lesiones purpúricas en cara y tórax, acompañadas de fiebre y vómitos con estrías de sangre. Se le indicó copa cónica en heces fecales y se observaron larvas de Strongyloides stercoralis, la biopsia de piel arrojó edema del dermis papilar y focos hemorrágicos, lesiones que se pueden presentar en pacientes con infección por esta parasitosis. En la encuesta epidemiológica se comprobó que la paciente acostumbraba a andar sin calzado con frecuencia y se constataron las malas condiciones higiénico-sanitarias en el hogar. Este caso constituye el primer reporte de estrongiloidosis crónica en la provincia.

The case of a 15 year-old adolescent remitted to the parasitology consultation at Pediatric Specialties Polyclinic of Camagüey is described, by presenting a marked eosinophilia and purpuric lesions in face and thorax, accompanied by fever and vomits with striae of blood. It was indicated conical cup in feces and Strongyloides stercoralis larvae were observed, the skin biopsy showed edema of the papillary dermis and hemorrhagic focuses, lesions that can show up in patients with infection for this parasitosis. In the epidemiological survey was proved that the patient frequently used to walk without having no shoes and bad hygienic-sanitary conditions at home were verified. This case constitutes the first chronic strongyloidosis report in the province.

Inhibition of PCSK9 as a novel strategy for the treatment of hypercholesterolemia.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role controlling the levels of low-density lipoprotein (LDL) particles that circulate in the bloodstream. Several gain-of-function and loss-of-function mutations in the PCSK9 gene, which occur naturally, have been identified and linked to hypercholesterolemia and hypocholesterolemia, respectively. Studies have demonstrated that PCSK9 acts mainly by enhancing degradation of the LDL receptor (LDLR) protein in the liver. Inactivation of PCSK9 in mice reduces plasma cholesterol levels primarily by increasing hepatic expression of LDLR protein and thereby accelerating clearance of circulating LDL cholesterol. Since the loss of a functional PCSK9 in human is not associated with apparent deleterious effects, this protease is becoming an attractive target for lowering plasma LDL cholesterol levels either alone or in combination with statins.

Purified human chorionic gonadotropin induces apoptosis in breast cancer.

Agents that induce apoptosis in breast cancer cells have great potential to facilitate chemotherapeutic intervention and improve patient outcomes. In this study, the effects of injecting purified human chorionic gonadotropin (hCG) directly into human breast cancer xenografts grown in nude mice were examined. It was shown that intratumoral injection of purified hCG increased the apoptotic index in breast cancer xenografts. These results were supported by the findings that exposure of breast cancer cells to purified hCG decreased cell viability in five different breast cancer cell lines. In some of these cell lines, the effects of hCG in cell viability appear to correlate with activation/expression of the hCG/luteinizing hormone receptor. Preoperative apoptotic induction by factors such as purified hCG may improve local control or work synergistically with neoadjuvant chemotherapy to improve complete pathologic response of locally advanced breast cancer.

PCSK9: an enigmatic protease.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role in cholesterol metabolism by controlling the levels of low density lipoprotein (LDL) particles that circulate in the bloodstream. Several gain-of-function and loss-of-function mutations in the PCSK9 gene, that occur naturally, have been identified and linked to hypercholesterolemia and hypocholesterolemia, respectively. PCSK9 expression has been shown to be regulated by sterol regulatory element binding proteins (SREBPs) and statins similar to other genes involved in cholesterol homeostasis. The most critical finding concerning PCSK9 is that this protease is able to influence the number of LDL receptor molecules expressed on the cell surface. Studies have demonstrated that PCSK9 acts mainly by enhancing degradation of LDL receptor protein in the liver. Inactivation of PCSK9 in mice reduces plasma cholesterol levels primarily by increasing hepatic expression of LDL receptor protein and thereby accelerating clearance of circulating LDL cholesterol. The objective of this review is to summarize the current information related to the regulation and function of PCSK9 and to identify gaps in our present knowledge.

Lauric acid dependent enhancement in hepatic SCPx protein requires an insulin deficient environment.

Sterol carrier protein X (SCPx) is a peroxisomal protein with both lipid transfer and thiolase activity. Treating with the fatty acid, lauric acid, induced SCPx mRNA levels in rat liver and in rat hepatoma H4IIE cells but enhanced protein levels of SCPx and the thiolase produced as a post-translational modification of SCPx were only seen in H4IIE cells. Further investigation revealed that the presence of insulin can mask lauric acid effects on the SCPx gene especially at the protein level. These data are in agreement with the findings that diabetes, a medical condition characterized by high levels of fatty acids in an insulin deficient environment, enhances the hepatic expression of SCPx.