HPX
Hemopexin precursor (Beta-1B-glycoprotein)
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Diagnostic tests able to reveal Alzheimer's disease (AD) in living patients before cognitive ability is destroyed are urgently needed. Such tests must distinguish AD from other dementia causes, as well as differentiate subtle changes associated with normal aging from true pathology emergence. A single biomarker offering such diagnostic and prognostic capacities has eluded identification. Therefore, a valuable test for AD is likely to be based on a specific pattern of change in a set of proteins, rather than a single protein. We examined pooled cerebrospinal fluid (CSF) samples obtained from neuropathologically-confirmed AD (n=43) and non-demented control subjects (n=43) using 2-dimensional gel electrophoresis (2DE) proteomic methodology to detect differentially expressed proteins. Proteins exhibiting expression level differences between the pools were recovered and identified using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry. Five differentially-expressed proteins with potential roles in amyloid-beta metabolism and vascular and brain physiology [apolipoprotein A-1 (Apo A-1), cathepsin D (CatD), hemopexin (HPX), transthyretin (TTR), and two pigment epithelium-derived factor (PEDF) isoforms] were identified. Apo A-1, CatD and TTR were significantly reduced in the AD pool sample, while HPX and the PEDF isoforms were increased in AD CSF. These results suggest that multi-factor proteomic pattern analysis of the CSF may provide a means to diagnose and assess AD.
MeSH Terms
- Aged
- Aged, 80 and over
- Aging
- Alzheimer Disease
- Amyloid beta-Peptides
- Apolipoprotein A-I
- Biomarkers
- Brain
- Cathepsin D
- Electrophoresis, Gel, Two-Dimensional
- Eye Proteins
- Female
- Hemopexin
- Humans
- Male
- Mass Spectrometry
- Nerve Growth Factors
- Nerve Tissue Proteins
- Prealbumin
- Predictive Value of Tests
- Proteomics
- Reference Values
- Serpins
The effects of dehydroepiandrosterone sulfate (DHEAS) on mimetic aging action of cultured neurons were studied in two models: the cultured cerebral cortex neurons were exposed to the xanthine oxidase-hypoxanthine(XO-HPX) system; serum free culture of cerebral cortex neurons. The results indicated that when cultured neurons were incubated for 6 h with XO-HPX system or 24 h serum free cultures, LDH release and MDA content increased while the number of surviving neurons decreased. The activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased and morphological injury developed. DHEAS (25, 50, 100 micrograms.L-1) concentration-dependently increased the number of surviving neurons and the activities of SOD and GSH-Px. It also inhibited the elevation of LDH and MDA induced by free radical and serum free cultures. The results suggest that DHEAS prevent the toxicity of free radical and serum free culture insults by suppressing the generation of lipid peroxide and increasing the activities of antioxidant enzymes.
MeSH Terms
- Aging
- Animals
- Cells, Cultured
- Cerebral Cortex
- Culture Media, Serum-Free
- Dehydroepiandrosterone Sulfate
- Female
- Fetus
- Glutathione Peroxidase
- L-Lactate Dehydrogenase
- Neurons
- Neuroprotective Agents
- Rats
- Rats, Wistar
- Superoxide Dismutase
We asked whether hypoxia and hypercapnia, singly or combined, affect the lung volume-dependent ventilatory inhibition [Hering-Breuer (HB) reflex] in newborn rats. Conscious rats 2, 5, and 8 days old were breathing in a flow plethysmograph. Mean lung volume was increased by applying a negative body surface pressure of 6 or 12 cmH2O. HB reflex was quantified as the inhibitory ratio (IR) of the apnea during the inflation expiratory time (TEinfl) to the control expiratory time (TEc), i.e., IR = TEinfl/TEc. In normoxia-normocapnia (control), IR with 6 cmH2O was approximately 8-12 at all ages and approximately doubled with inflation at 12 cmH2O. In hypoxia (HPX; 10% O2) or hypercapnia (HPCN; 3% CO2), IR decreased at 8 days, whereas it did not differ from the control value at 2 and 5 days. In HPX HPCN, IR decreased at all ages. In HPX (at both 6- and 12-cmH2O inflations), in HPCN (6 cmH2O), or in HPX HPCN (6 and 12 cmH2O), IR decreased significantly more at 8 days than at 2 days. Metabolic rate, simultaneously measured, decreased during HPX or HPX HPCN by a similar amount at all ages. The ventilatory response to HPX or to HPCN was significantly more pronounced at 8 days than at 2 days. We conclude that, during the early postnatal development of the rat, HPX or HPCN, singly or combined, reduces the HB reflex inhibition in the oldest pups, with minimal or no effects in the youngest. These developmental differences cannot be explained by differences in metabolic drive on ventilation but are contributed to by differences in chemosensitivity.
MeSH Terms
- Aging
- Animals
- Animals, Newborn
- Hypercapnia
- Hypoxia
- Lung Volume Measurements
- Oxygen Consumption
- Plethysmography
- Rats
- Rats, Sprague-Dawley
- Reflex, Stretch
- Respiratory Mechanics
- Vagus Nerve