Psychological or physical stress induces an elevation of corticosteroids in the circulating system. We report here that corticosterone (CT) protects cardiomyocytes from apoptotic cell death induced by doxorubicin (Dox), an antineoplastic drug known to induce cardiomyopathy possibly through reactive oxygen species production. The cytoprotection induced by CT is within the range of physiologically relevant doses. The lowest dose tested, 0.1 M (or 3.5 g/dl), inhibited apoptosis by approximately 25% as determined by caspase activity. With 1 M CT, cardiomyocytes gain a cytoprotective effect after 8 h of incubation and remain protected for at least 72 h. Hydrocortisone, cortisone, dexamethasone, and aldosterone but not androstenedione or cholesterol also induced cytoprotection. Analyses of 20,000 gene expression sequences using Affymetrix high-density oligonucleotide array found that CT caused up-regulation of 140 genes and down-regulation of 108 genes over 1.5-fold. Among the up-regulated genes are bcl-xL, metallothioneins, glutathione peroxidase-3, and glutathione Stransferases. Western blot analyses revealed that CT induced an elevation of bcl-xL but not bcl-2 or proapoptotic factors bax, bak, and bad. Inhibiting the expression of bcl-xL reduced the cytoprotective effect of CT. Our data suggest that CT induces a cytoprotective effect on cardiomyocytes in association with reprogramming gene expression and induction of bcl-xL gene.
Fibroblasts are the most ubiquitous cell types within our body. They produce various factors to maintain the texture and structure of a particular organ or tissue. To identify protein factors secreted by fibroblasts and alteration of these protein factors upon oxidative stress, HCA 3 human skin diploid fibroblasts were exposed to a sublethal dose of H 2 O 2 , which induces a prematurely senescent phenotype. Conditioned media from prematurely senescent cells versus control cells were analyzed for proteins using an LC-MS/MS-based proteomic technique. Collagen ␣1(VI), collagen ␣2(I), fibronectin, lumican, and matrix metalloproteinase 2 were among the proteins consistently detected from control and H
Drought is one of the most severe abiotic stresses, the damage due to which, various plant species mitigate by activating mechanisms that are not yet well understood. Caragana korshinskii is a xerophytic shrub found in the semi-arid regions of northwest China with high tolerance to several abiotic stresses, including drought. Based on the de novo transcriptome data from C. korshinskii leaflets collected along a precipitation gradient on the Loess Plateau (China), most of the differentially expressed genes were explored using trend analysis along the precipitation gradient. Gene ontological analysis showed that "phenylpropanoid biosynthesis process ! secondary metabolite biosynthetic process" terms were the most significant gene ontologies, whereas Kyoto Encyclopedia of Genes and Genomes-based analysis indicated that the biosynthesis of secondary metabolites was a significant metabolic pathway. Real-time polymerase chain reaction and enzyme activity analyses confirmed the increased transcription of the phenylalanine ammonialyase (PAL) gene in C. korshinskii under drought stress in field and laboratory conditions. These results suggested that C. korshinskii adjusts its secondary metabolism to water-deficit environments and activates PAL by drought stress. Therefore, further studies on the obtained data can expand the current understanding of the molecular and genetic mechanisms responsible for the drought endurance in C. korshinskii.
Background:Type 2 diabetes mellitus (T2DM) has traditionally been considered to affect mainly the elderly; however, the age at diagnosis has gradually reduced in recent years. Although the incidence of young-onset T2DM is increasing, it is still not fully clear the onset characteristics and risk factors of early-onset T2DM. The aim of this study was to describe the initiating characteristics of early-onset T2DM in Chinese patients and evaluate the risk factors for diabetes mellitus.Methods:This cross-sectional controlled study was performed using a questionnaire survey method in outpatients of multiple centers in China. A total of 1545 patients with T2DM with an age at onset of <40 years were included, and the control group consisted of subjects aged <40 years with normal blood glucose level.Results:In patients with young-onset T2DM, the mean age and initial hemoglobin 1Ac at diagnosis were 32.96 ± 5.40 years and 9.59 ± 2.71%, respectively. Most of the patients were obese, followed irregular diet pattern and sedentary lifestyle, had life or work pressure, and had a family history of diabetes mellitus. Compared with subjects with normal blood glucose level, logistic regression analysis showed that waist-to-hip ratio (odds ratio [OR] 446.99, 95% confidence interval [CI] 42.37–4714.87), family history of diabetes mellitus (OR 23.46, CI 14.47–38.03), dyslipidemia (OR 2.65, CI 1.54–4.56), diastolic blood pressure (OR 1.02, CI 1.00–1.04), and body mass index (OR 0.95, CI 0.92–0.99) are independent factors for early-onset T2DM.Conclusions:We observed that abdominal obesity, family history of diabetes mellitus, and medical history of hypertension and dyslipidemia are independent risk factors for early-onset T2DM. It is, therefore, necessary to apply early lifestyle intervention in young people with risk of diabetes mellitus.
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