STMN1
Stathmin (Leukemia-associated phosphoprotein p18) (Metablastin) (Oncoprotein 18) (Op18) (Phosphoprotein p19) (pp19) (Prosolin) (Protein Pr22) (pp17) [C1orf215] [LAP18] [OP18]
Publications[править]
Major depressive disorder (MDD) is frequently associated with chronic medical illness responsible of increased disability and mortality. Inflammation and oxidative stress are considered to be the major mediators of the allostatic load, and has been shown to correlate with telomere erosion in the leucocytes of MDD patients, leading to the model of accelerated aging. However, the significance of telomere length as an exclusive biomarker of aging has been questioned on both methodological and biological grounds. Furthermore, telomeres significantly shorten only in patients with long lasting MDD. Sensitive and dynamic functional biomarkers of aging would be clinically useful to evaluate the somatic impact of MDD. To address this issue we have measured in the blood leucocytes of MDD patients (N=17) and controls (N=16) the expression of two genes identified as robust biomarkers of human aging and telomere dysfunction: p16(INK4a) and STMN1. We have also quantified the transcripts of genes involved in the repair of oxidative DNA damage at telomeres (OGG1), telomere regulation and elongation (TERT), and in the response to biopsychological stress (FOS and DUSP1). The OGG1, p16(INK4a), and STMN1 gene were significantly up-regulated (25 to 100%) in the leucocytes of MDD patients. Expression of p16(INK4a) and STMN1 was directly correlated with anxiety scores in the depression group, and that of p16(INK4a), STMN and TERT with the depression and anxiety scores in the combined sample (MDD plus controls). Furthermore, we identified a unique correlative pattern of gene expression in the leucocytes of MDD subjects. Expression of p16(INK4) and STMN1 is a promising biomarker for future epidemiological assessment of the somatic impact of depressive and anxious symptoms, at both clinical and subclinical level in both depressive patients and general population.
MeSH Terms
- Adult
- Aging
- Anxiety
- Biomarkers
- Cellular Senescence
- Cyclin-Dependent Kinase Inhibitor p16
- DNA
- DNA Damage
- Depression
- Depressive Disorder, Major
- Female
- Gene Expression Regulation
- Humans
- Leukocytes
- Middle Aged
- Oxygen
- Stathmin
- Telomere
- Up-Regulation
In the normal brain, age is associated with changes in gene expression. Age is also a prominent risk factor for Alzheimer's disease (AD), where clinical features are similar to age-related decreases in cognitive performance. We hypothesized that some age-related changes in gene expression are accelerated in AD patients. To study this, we selected 10 candidate genes earlier shown by microarray analysis to be differentially expressed in AD (Emilsson et al., [2006] Neurobiol Dis 21:618-625). Using real-time PCR analysis and a control based statistical model, we investigated age-related changes in mRNA levels in a large collection of human brain postmortem tissues from AD patients and controls. Our results demonstrate that the age-related changes in gene expression are manifested earlier in AD. Furthermore, five of the genes (ITPKB, RGS4, RAB3A, STMN1, SYNGR3) have in common an involvement in neuronal calcium dependent signaling, a cellular process previously related to both AD and aging. These observations suggest that coordinated transcriptional changes associated with ageing and calcium homeostasis in the human brain are accelerated in patients with AD. Our results point to the possibility that the activity of these genes can be used in the future as a palette of biomarkers for predicting disease risk in young individuals.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Female
- Gene Expression Profiling
- Gene Expression Regulation
- Humans
- Male
- Membrane Proteins
- Middle Aged
- Nerve Tissue Proteins
- Oligonucleotide Array Sequence Analysis
- Phosphotransferases (Alcohol Group Acceptor)
- RGS Proteins
- Stathmin
- Synaptogyrins
- rab3A GTP-Binding Protein
Expression levels of 33 high egg production candidate transcripts in Red-feather Taiwan country chickens (TCCs) were examined by quantitative reverse-transcription (RT) polymerase chain reactions (PCR) in this study. Candidate transcripts were previously identified from a L2-B (L2-subtract-B) hypothalamus/pituitary gland subtractive cDNA library. In this subtractive cDNA library, two divergently selected strains of TCCs, B and L2 were used. These two strains were originated from one single population and were further subjected (since 1982) to the selections of body weight/comb size (B) and eggs to 40wk of age (L2), respectively. Hypothalamuses and pituitary glands that sampled from Red-feather TCCs were previously grouped into high (Red-high; n=20) and low (Red-low; n=20) egg productions based on the rate of lay after 1st egg (hen-day laying rate; %). Rates of lay after 1st egg (mean /-S.E.) in the Red-high and the Red-low subpopulations were 72.2 /-0.6 and 23.0 /-3.5, respectively (P<0.01). Quantitative RT-PCR validated that 25 candidate transcripts were significantly higher expressed in the Red-high than in the Red-low hens. These transcripts were ANP32A, BDH, CDC42, CNTN1, COMT, CPE, CTNNB1, DIO2, EIF4E, GARNL1, HSPCA, LAPTM4B, MBP, NAP1L4, NCAM1, PARK7, PCDHA@, PGDS, PLAG1, PRL, RAD21, SAR1A, SCG2, STMN1 and UFM1. Among these transcripts, 15 (79.0%), 13 (68.4%), and 12 (63.2%) genes were annotated to involve in cellular physiological process (GO:0050875), metabolism (GO:0008152) and cell communication (GO:0007154). Identified transcripts that related to high egg production are most active in focal adhesion, adherens junction, MAPK signaling, tight junction and cell adhesion pathways.
MeSH Terms
- Aging
- Animals
- Chickens
- Color
- Feathers
- Female
- Gene Expression Profiling
- Gene Expression Regulation
- Hypothalamus
- Oviposition
- Pituitary Gland
- Taiwan
- Transcription, Genetic