Sex differences in mitochondrial numbers and function are present in large cerebral arteries, but it is unclear whether these differences extend to the microcirculation. We performed an assessment of mitochondria-related proteins in cerebral microvessels (MVs) isolated from young, male and female, Sprague-Dawley rats. MVs composed of arterioles, capillaries, and venules were isolated from the cerebrum and used to perform a 3 versus 3 quantitative, multiplexed proteomics experiment utilizing tandem mass tags (TMT), coupled with liquid chromatography/mass spectrometry (LC/MS). MS data and bioinformatic analyses were performed using Proteome Discoverer version 2.2 and Ingenuity Pathway Analysis. We identified a total of 1969 proteins, of which 1871 were quantified by TMT labels. Sixty-four proteins were expressed significantly (p < 0.05) higher in female samples compared with male samples. Females expressed more mitochondrial proteins involved in energy production, mitochondrial membrane structure, anti-oxidant enzyme proteins, and those involved in fatty acid oxidation. Conversely, males had higher expression levels of mitochondria-destructive proteins. Our findings reveal, for the first time, the full extent of sexual dimorphism in the mitochondrial metabolic protein profiles of MVs, which may contribute to sex-dependent cerebrovascular and neurological pathologies. 相似文献
Virginia G. Kaklamani, MD, DSc; Kari B. Wisinski, MD; Maureen Sadim, BS; Cassandra Gulden, MS; Albert Do, BS; Kenneth Offit, MD, MPH; John A. Baron, MD; Habibul Ahsan, MD, MPH; Christos Mantzoros, MD, MPH; Boris Pasche, MD, PhD
JAMA. 2008;300(13):1523-1531.
Context Current epidemiological evidence suggests an associationbetween obesity, hyperinsulinemia, and colorectal cancer risk.Adiponectin is a hormone secreted by the adipose tissue, andserum levels are inversely correlated with obesity and hyperinsulinemia.While there is evidence of an association between circulatingadiponectin levels and colorectal cancer risk, no associationbetween genes of the adiponectin pathway and colorectal cancerhave been reported to date.
Objective To determine the association of 10 haplotype-taggingsingle-nucleotide polymorphisms (SNPs) of the adiponectin (ADIPOQ)and adiponectin receptor 1 (ADIPOR1) genes with colorectal cancerrisk.
Design, Setting, and Patients Two case-control studiesincluding patients with a diagnosis of colorectal cancer andcontrols were recruited between 2000 and 2007. Case-controlstudy 1 included a total of 441 patients with a diagnosis ofcolorectal cancer and 658 controls; both groups were of AshkenaziJewish ancestry and from New York, New York. Case-control study2 included 199 patients with a diagnosis of colorectal cancerand 199 controls from Chicago, Illinois, matched 1:1 for sex,age, and ethnicity.
Main Outcome Measures ADIPOQ and ADIPOR1 SNP frequencyamong cases and controls.
Results In study 1, after adjustment for age, sex, andSNPs from the same gene, 3 ADIPOQ SNPs and 1 ADIPOR1 SNP wereassociated with colorectal cancer risk: rs266729 (adjusted oddsratio [AOR], 0.72; 95% confidence interval [CI], 0.55-0.95)and rs822396 (AOR, 0.37; 95% CI, 0.14-1.00) were associatedwith decreased risk whereas rs822395 (AOR, 1.76; 95% CI, 1.09-2.84)and rs1342387 (AOR, 1.79; 95% CI, 1.18-2.72) were associatedwith increased risk. In study 2, after adjustment for age, sex,race, and SNPs from the same gene, the ADIPOQ SNP rs266729 wasassociated with a decreased colorectal cancer risk of similarmagnitude as in study 1 (AOR, 0.52; 95% CI, 0.34-0.78). Combinedanalysis of both studies shows an association of rs266729 withdecreased colorectal cancer risk (AOR, 0.73; 95% CI, 0.53-0.99).
Conclusion The SNP rs266729, which tags the 5' flankingregion of the ADIPOQ gene, is associated with decreased colorectalcancer risk.
Obesity has been shown to increase breast cancer risk. FTO is a novel gene which has been identified through genome wide association studies (GWAS) to be related to obesity. Our objective
was to evaluate tissue expression of FTO in breast and the role of FTO SNPs in predicting breast cancer risk. 相似文献
