ABSTRACT
This study aimed to investigate the effect of Jiaotai Pills on protein expression in the hippocampus of the rat model of chronic unpredictable mild stress(CUMS)-induced depression by quantitative proteomics and explore the anti-depression mechanism of Jiaotai Pills. The SD rats were randomized into control, model, Jiaotai Pills, and fluoxetine groups(n=8). Other groups except the control group were subjected to CUMS modeling for 4 weeks. After 4 weeks of continuous administration, the changes of behavior and pathological morphology of the hippocampal tissue were observed. Proteins were extracted from the hippocampal tissue, and bioinformatics analysis was performed for the differentially expressed proteins(DEPs) identified by quantitative proteomics. Western blot was employed to verify the key DEPs. The results showed that Jiaotai Pills significantly alleviated the depression behaviors and hippocampal histopathological changes in the rat model of CUMS-induced depression. A total of 5 412 proteins were identified in the hippocampus of rats, including 65 DEPs between the control group and the model group and 35 DEPs between the Jiaotai Pills group and the model group. There were 16 DEPs with the same trend in the Jiaotai Pills group and the control group, which were mainly involved in sphingolipid, AMPK, and dopaminergic synapse signaling pathways. The Western blot results of Ppp2r2b, Cers1, and Ndufv3 in the hippocampus were consistent with the results of proteomics. In conclusion, Jiaotai Pills may play an anti-depression role by modulating the levels of Ppp2r2b, Cers1, Ndufv3 and other proteins and regulating sphingolipid, AMPK, and dopaminergic synapse signaling pathways.
Subject(s)
Rats , Animals , Rats, Sprague-Dawley , Depression/drug therapy , AMP-Activated Protein Kinases/metabolism , Proteomics , Hippocampus , Stress, Psychological/metabolism , Sphingolipids/metabolism , Disease Models, Animal , Drugs, Chinese HerbalABSTRACT
El cáncer de vejiga representa un problema de salud pública importante a nivel mundial. En Chile su relevancia es aún mayor en la región de Antofagasta. Este cáncer se caracteriza por una alta tasa de recurrencia, por lo que los pacientes requieren un seguimiento estricto que afecta su calidad de vida e implica elevados costos para los sistemas de salud. Esto explica la necesidad de optimizar los tratamientos actuales (quimioterapia e inmunoterapia con BCG intravesical) para reducir las tasas de recurrencia y progresión. Los esfingolípidos son lípidos bioactivos que a nivel celular cumplen funciones relacionadas con la regulación del crecimiento, proliferación, migración, invasión, resistencia a drogas y apoptosis. La evidencia disponible a la fecha sobre el rol de los esfingolípidos en cáncer de vejiga es escasa, pero sugiere que en este cáncer existe un metabolismo esfingolipídico desplazado hacia la reducción de los niveles intracelulares de ceramida y esfingosina (esfingolípidos pro-apoptóticos) y aumento de esfingosina 1-fosfato (esfingolípido anti-apoptótico). La manipulación del metabolismo esfingolipídico para invertir esta relación se propone en esta revisión como una estrategia que podría ayudar a optimizar el efecto de las terapias disponibles actualmente para reducir las recurrencias y progresiones de los tumores de vejiga no músculo-invasores...
Bladder cancer is an important health problem worldwide. In Chile it has particular relevance in the region of Antofagasta. This cancer is characterized by a high recurrence rate, for which patients need a strict follow up that impairs their quality of life and determines increased costs for health care systems. These facts explain the necessity of optimizing the actual treatments (chemotherapy and BCG immunotherapy) for reducing the rates of recurrence and progression. Sphingolipids are bioactive lipids that at a cellular level have roles related to the regulation of growth, proliferation, migration, invasiveness, drug resistance and apoptosis. To date, the available evidence about the role of sphingolipids in bladder cancer is scarce, but suggests that in this cancer there is a sphingolipid metabolism shifted towards a reduction of the intracellular levels of ceramide and sphingosine (pro-apoptotic sphingolipids) and an increase of sphingosine 1-phosphate (anti-apoptotic sphingolipid). In this review we propose that the manipulation of the sphingolipid metabolism to invert this balance can contribute to optimize the effect of the actual therapies to reduce the rates of recurrence and progression of non-muscle invasive bladder cancers...
Subject(s)
Humans , Sphingolipids/metabolism , Sphingolipids/therapeutic use , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/drug therapyABSTRACT
Las fumonisinas son una familia de micotoxinas que contaminan al maíz, alteran el metabolismo de los esfingolípidos y del folato, se asocian con defectos del tubo neural y están catalogadas por la Agencia Internacional de Investigación en Cáncer (IARC por sus siglas en inglés) como posibles carcinógenos humanos. Debido a que en México los derivados de maíz constituyen una parte importante de la dieta y existe alta prevalencia de población genéticamente susceptible a la deficiencia de folato, en este ensayo se presentan las evidencias mundiales y nacionales de la exposición a fumonisinas y la relevancia que para México representa la evaluación de esta exposición.
Fumonisins are mycotoxins that contaminate maize, disrupt the folate and sphingolipid metabolism, are associated with neural tube defects, and are considered by the International Agency for Research on Cancer (IARC) as possible human carcinogens. Since maize-based foods are significant components of the Mexican diet and there is a high prevalence of genetic susceptibility for folate deficiency among Mexicans, this essay presents international and national evidence of fumonisin exposure and the relevance that such exposure represents for Mexico.
Subject(s)
Adolescent , Adult , Animals , Female , Humans , Male , Mice , Pregnancy , Rats , Young Adult , Folic Acid/metabolism , Food Contamination , Fumonisins/adverse effects , Neural Tube Defects/etiology , Carcinogens, Environmental/adverse effects , Digestive System Neoplasms/chemically induced , Digestive System Neoplasms/epidemiology , Equidae , /antagonists & inhibitors , Fumonisins/chemistry , Fumonisins/pharmacokinetics , Fumonisins/toxicity , Homocystinuria/epidemiology , Homocystinuria/genetics , Kidney Tubular Necrosis, Acute/chemically induced , Leukoencephalopathies/chemically induced , Leukoencephalopathies/veterinary , Membrane Transport Proteins/metabolism , /deficiency , /genetics , Mexico , Muscle Spasticity/epidemiology , Muscle Spasticity/genetics , Neural Tube Defects/chemically induced , Neural Tube Defects/epidemiology , Neural Tube Defects/genetics , Psychotic Disorders/epidemiology , Psychotic Disorders/genetics , Sphingolipids/chemistry , Sphingolipids/metabolism , Swine , Teratogens/toxicity , Young Adult , Zea mays/microbiologyABSTRACT
Abstract Phospholipase D (PLD) plays an important role as an effector in a variety of physiological processes that reveal it to be a member of the signal transducing phospholipases. Recently, PLD2 was reported as a necessary intermediate in preventing apoptosis induced by hydrogen peroxide or hypoxia in rat pheochromocytoma (PC12) cells. The data presented here show that both PLD isozymes, PLD1 and PLD2 are also required in attenuating glutamate-induced cell death in PC12 cells. Treatment of PC12 cells with glutamate resulted in induction of apoptosis in these cells, which is accompanied by decreased PLD activity and increased ceramide concentration. Incubation of PC12 cells with exogenous C6-ceramide showed a time-dependent decrease of PLD activity. When cDNAs of PLD1 and PLD2 were transfected into PC12 cells respectively, overexpression of PLD1 or PLD2 resulted in inhibition of glutamate-induced apoptotic cell death. These data indicate that both PLD1 and PLD2 play a protective role against glutamate-induced cell death in PC12 cells.