Effects of aging on protein expression in mice brain microvessels: ROS scavengers, mRNA/protein stability, glycolytic enzymes, mitochondrial complexes, and basement membrane components.
Effects of aging on protein expression in mice brain microvessels: ROS scavengers, mRNA/protein stability, glycolytic enzymes, mitochondrial complexes, and basement membrane components.
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DOI：
10.1007/s11357-021-00468-1
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发表时间：
2022-03
期刊：
影响因子：
5.6
通讯作者：
Busija DW
中科院分区：
文献类型：
--
作者：
Chandra PK;Cikic S;Rutkai I;Guidry JJ;Katakam PVG;Mostany R;Busija DW
采用基于发现的蛋白质组学分析方法对年轻、中年和老年雄性和雌性小鼠皮质微血管（mv）中的差异表达（DE）蛋白进行了评估（> 4,200个定量蛋白/组）。大多数DE蛋白（> 90%）在性别间无显著差异；然而，在MVs中显示性别差异的一些重要DE蛋白从年轻小鼠（8.3%）到中年小鼠（3.7%）和老年小鼠（0.5%）下降。因此，我们将男性和女性数据结合起来进行年龄相关的比较，但在检查时注意到性别差异。参与氧化应激反应的关键蛋白、mRNA或蛋白稳定性、基底膜（BM）组成、有氧糖酵解和线粒体功能随着年龄的增长而显著改变。随着年龄的增长，超氧化物歧化酶-1/-2、过氧化氢酶和硫氧还蛋白的相对丰度降低。参与mRNA降解或mRNA前剪接的蛋白在老年小鼠mv中显著增加，而蛋白质稳定蛋白则减少。糖酵解蛋白在中年时不受影响，但这些蛋白的相对丰度在老年小鼠的MVs中下降。尽管构成线粒体复合体I-V的41种蛋白质中的大多数在老年小鼠中减少，但其中6种蛋白质在中年小鼠中显着减少，但14种蛋白质的相对丰度增加。Nidogen、胶原蛋白和层粘连蛋白家族成员以及perlecan在衰老过程中表现出不同的模式，表明BM重组始于中年。我们认为，衰老过程中氧化应激的增加会导致脑皮层MVs蛋白谱的不利变化，从而影响mRNA/蛋白的稳定性、脑基质的完整性和ATP的合成能力。在线版本包含补充材料，可在10.1007/s11357-021-00468-1获得。
Differentially expressed (DE) proteins in the cortical microvessels (MVs) of young, middle-aged, and old male and female mice were evaluated using discovery-based proteomics analysis (> 4,200 quantified proteins/group). Most DE proteins (> 90%) showed no significant differences between the sexes; however, some significant DE proteins showing sexual differences in MVs decreased from young (8.3%), to middle-aged (3.7%), to old (0.5%) mice. Therefore, we combined male and female data for age-dependent comparisons but noted sex differences for examination. Key proteins involved in the oxidative stress response, mRNA or protein stability, basement membrane (BM) composition, aerobic glycolysis, and mitochondrial function were significantly altered with aging. Relative abundance of superoxide dismutase-1/-2, catalase and thioredoxin were reduced with aging. Proteins participating in either mRNA degradation or pre-mRNA splicing were significantly increased in old mice MVs, whereas protein stabilizing proteins decreased. Glycolytic proteins were not affected in middle age, but the relative abundance of these proteins decreased in MVs of old mice. Although most of the 41 examined proteins composing mitochondrial complexes I–V were reduced in old mice, six of these proteins showed a significant reduction in middle-aged mice, but the relative abundance increased in fourteen proteins. Nidogen, collagen, and laminin family members as well as perlecan showed differing patterns during aging, indicating BM reorganization starting in middle age. We suggest that increased oxidative stress during aging leads to adverse protein profile changes of brain cortical MVs that affect mRNA/protein stability, BM integrity, and ATP synthesis capacity. The online version contains supplementary material available at 10.1007/s11357-021-00468-1.
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DOI：
10.1177/0271678x21999553
发表时间：
2021-09
期刊：
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism
影响因子：
--
作者：
Chandra PK;Cikic S;Baddoo MC;Rutkai I;Guidry JJ;Flemington EK;Katakam PV;Busija DW
通讯作者：
Busija DW
影响因子：
6.9
作者：
Candiello, Joseph;Cole, Gregory J.;Halfter, Willi
通讯作者：
Halfter, Willi
影响因子：
4.2
作者：
BUCHWEITZMILTON, E;WEISS, HR
通讯作者：
WEISS, HR
影响因子：
11.1
作者：
Eichmann, Anne;Simons, Michael
通讯作者：
Simons, Michael
影响因子：
4.2
作者：
BELL, MA;BALL, MJ
通讯作者：
BALL, MJ