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ALTERATIONS OF ZINC TRANSPORTERS IN ALZHEIMER'S DISEASELyubartseva, Ganna 01 January 2009 (has links)
Alzheimer’s disease (AD), one of the major causes of disability and mortality in Western societies, is a progressive age-related neurodegenerative disorder. Increasing evidence suggests the etiology of AD may involve disruptions of zinc (Zn) homeostasis. We hypothesize that disruption of Zn homeostasis leads to alterations of Zn transporter (ZnT) proteins, resulting in increased production of neurotoxic amyloid beta (Aβ) peptide in AD brain. To address this hypothesis we carried out the following studies.
1. We characterized alterations of ZnT-1, ZnT-4 and ZnT-6 in the brain of preclinical AD (PCAD) subjects, who show no overt clinical manifestations of AD but demonstrate significant AD pathology at autopsy.
2. We identified the presence of ZnT-2 in human brain and compared protein levels in the brains of subjects with PCAD, mild cognitive impairment (MCI), early (EAD), and late-stage AD (LAD) to those in age matched normal control (NC) subjects.
3. We examined the relationship between protein levels of ZnT-1, ZnT-2, ZnT-4, ZnT-6 and Aβ produced by H4 human neuroglioma cells (H4-APP) transfected to overexpress amyloid precursor protein (APP), treated with short interfering RNA (siRNA) against each ZnT.
Our data show a significant decrease (P < 0.05) of ZnT-1 and a significant increase of ZnT-6 in hippocampus/parahippo-campal gyrus (HPG) of PCAD subjects. In PCAD cerebellum (CER) the data show a significant increase of ZnT-4 and ZnT-6 compared to NC subjects. Levels of ZnT-2 were also significantly decreased in HPG of PCAD subjects compared to NC subjects. In addition, levels of ZnT-2 were significantly (P < 0.05) elevated in SMTG of PCAD and MCI subjects, compared to NC subjects. ZnT-2 was significantly (P < 0.05) elevated in HPG of EAD and LAD, and in SMTG of LAD brains, but was significantly (P < 0.05) decreased in LAD CER compared to NC subjects. siRNA mediated attenuation of each ZnT protein studied (ZnT-2, ZnT-4 and ZnT-6) led to significantly (P < 0.05) decreased production of Aβ compared to controls.
Our results suggest alterations in Zn transport may play a role in Aβ processing and contribute to the neuropathology of AD.
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Παρασκευή και πιστοποίηση ζωοτροφής για πειραματική μελέτη των επιδράσεων των μετάλλων στις λιπιδαιμίεςΛέκκας, Παναγιώτης 21 July 2015 (has links)
O ψευδάργυρος -Zn ελέγχει τον μεταβολισμό των λιπιδίων και γλυκόζης μέσω Ζn-μεταγραφικών παραγόντων. Δίαιτες υψηλών λιπαρών οδηγούν στην ενδοκυτταρική συσσώρευση ελευθέρων ριζών, μειώνουν την μεταγραφική έκφραση των εκκαθαριστών τους και την ενεργότητα αντιοξειδωτικών ενζύμων και οδηγούν σε μεταβολικό σύνδρομο. Οι πρωτεϊνες του θερμικού shock (Heat shock proteins-HSP) παίζουν σημαντικό ρόλο στην αντίσταση στο κυτταρικό stress ως προσαρμογή ,μετά από έκθεση, σε διάφορα ερεθίσματα.
ΣΚΟΠΟΣ : Μελέτη της επίδρασης του διατροφικού Ζn και των Hsp70,στην μεταβονομική των λιπιδίων αίματος και ήπατος ποντικών
ΥΛΙΚΟ-ΜΕΘΟΔΟΙ :Ενήλικα αρσενικά ποντίκια: 1. Wild type (Wt) Hybrid (F1/F1) C57Bl/6 x CBA και 2. Transgenic (Tg) human HSP70 overexpressing mice, από ηλικίας ενός μηνός εντάχθηκαν στις παρακάτω διατροφές ,επί 10 εβδομάδες.
Διατροφή Αριθμός Wt Αριθμός Tg
Chow Diet (30 Zn) 6 10
High Fat Diet (3 Zn) 13 12
High Fat Diet (30 Zn) 9 8
High Fat Diet (300 Zn) 12 12
Σύνθεση των τριών διαιτών υψηλών λιπαρών -HFD: 3mg, 30mg, 300mg Zn /kg τροφής (mucedoola s.r.l Ιtaly-55% Cal από λιπαρά στοιχεία), Chow : δίαιτα ελέγχου
Βιοχημικές αναλύσεις: Cholesterol ,Triglycerides ,HDL-cholesterol, Glucose ,Insulin
Μετρήσεις μετάλλων και αντιοξειδωτικών παραγόντων: SOD (ερυθρά αιμοσφαίρια ) TAC (ορός αίματος) Zn , Cu (ερυθρά αιμοσφαίρια και ιστός ήπατος)
Μεταβονομική ανάλυση και αξιολόγηση λιπιδίων :Εκχύλιση ορού αίματος και ηπατικού ιστού για λήψη Φάσματος 1H-NMR
ΣΥΜΠΕΡΑΣΜΑΤΑ
1. Η HF δίαιτα αύξησε σημαντικά ,το τελικό βάρος και τον ρυθμό αύξησης βάρους ,τη χοληστερόλη -CL και την λιποπρωτεϊνη υψηλής πυκνότητας-ΗDL ,την ινσουλίνη –Ins, στα WT & Tg και μείωσε την ολική αντιοξειδωτική ικανότητα-TAC στο πλάσμα και την δραστηριότητα της σουπεροξείδιο-δισμουτάσης-SOD στα ερυθροκύταρα των WΤ και Tg
2. Ο επαρκής διατροφικός Zn (30mg/kgτροφής) φαίνεται να αποτελεί κρίσιμο παράγοντα διαμόρφωσης προστατευτικού ηπατολιπιδαιμικού προφίλ, ποντικών σε υπερλιπιδική δίαιτα.
Η αύξηση ή μείωση του Zn σε HFDς φαίνεται να μειώνει την TAC του πλάσματος σε WΤ και Tg ενώ η δραστικότητα της SOD φαίνεται ανάλογη των επιπέδων του Zn
Η ανεπάρκεια ή περίσσεια Zn αυξάνει τα αθηρογόνα SFA και μειώνει τα αντι-αθηρογόνα λιπίδια, PC, DU, LA DIAL ,UFA στις HDL, nonHDL και το ήπαρ, στα WΤHFD και στα ΤgHFD
3. Οι HSP70 : Τα διαγονιδιακά ζώα που φέρουν το γονίδιο hHsp70, φαίνεται ότι είτε σε έλλειψη είτε σε περίσσεια Ζn, που συνήθως συνοδεύoνται από μεταβολικό σύνδρομο, κατορθώνουν να διατηρούν καλλίτερους δείκτες λιπιδικού προφίλ σε σχέση με τα WT ζώα.
Τα Τg εμφάνισαν σημαντικά χαμηλότερη CL ,TG , HDL σε σύγκριση με τα WT ενώ η HSP70 αύξησε σημαντικά την ενεργότητα της ολικής SOD στα ερυθρά αιμοσφαίρια.
Η HSP70 μείωσε τα αθηρογόνα SFA και αύξησε τα αντιαθηρογόνα λιπίδια DIAL, DU, LA, UFA, SM στις HDL, nonHDL , και στο ήπαρ ποντικών που εκτέθηκαν σε HFD και σε όλες τις συγκεντρώσεις Zn. / Zinc –Zn controls lipid and glucose metabolism via Zn-transcription factors. High fat diets –HFDs lead to intracellular free radicals accumulation, decrease the transcriptional expression of their scavengers and anti-oxidative enzymes’ activity leading finally to metabolic syndrome. Heat shock proteins-HSPs play a significant role in cellular resistance response , as an adaptation mechanism, after exposure to various stimuli.
SCOPE: To study the effects of nutritional Zn and HSP70s on the metabonomics of serum and liver lipids in mice
MATERIALS-METHODS: Male mice: 1. Wild type (Wt) Hybrid (F1/F1) C57Bl/6 x CBA και 2. Transgenic (Tg) human HSP70 overexpressing mice, one month old, were subjected for 10 weeks to the following diets :
Diet Number of Wt Number of Tg
Chow Diet (30 Zn) 6 10
High Fat Diet (3 Zn) 13 12
High Fat Diet (30 Zn) 9 8
High Fat Diet (300 Zn) 12 12
Composition of the three HF Diets: 3mg, 30mg, 300mg Zn /kg τροφής (mucedoola s.r.l Ιtaly-55% Cal from greasy ingredients),Chow :control diet
Biochemical analyses: Cholesterol ,Triglycerides ,HDL-cholesterol, Glucose ,Insulin
Metals and antioxidative factors levels: SOD (red blood cells )TAC (blood serum) Zn , Cu (red blood cells and liver tissue)
Lipids metabonomics : Blood serum and liver tissue extracts for 1H-NMR spectrum analysis and evaluation
CONCLUSIONS
1. HFDiet significantly increased the rate of mice body weight gaining, as well as, cholesterol-CL, high density lipoproteins-HDL, insulin, in WT and Tg mice and decreased plasma total antioxidant capacity-TAC and red blood cell super oxide dismutase –SOD activity , in WT and Tg mice
2.Suficient nutritional Zn (30 mg/kg food) prevails as a crucial modulator of a protective hepato-lipidaemic profil of mice in high fat diet.
Zinc deficiency or excessiveness , in HFDiets , decreases plasma TAC in WT and Tg mice, while SOD activity shows proportional to Zn levels.
Zinc deficiency or excessiveness increases the atherogenic SFA and decreases the anti –atherogenic lipids : PC, DU, LA DIAL ,UFA, in HDL, nonHDL and liver, in WΤ-HFD and Τg-HFD mice
3. HSP70s : Transgenic mice over-expressing hHsp70 gene and exposed either to Zn deficiency or Zn excessiveness , both driving usually to metabolic syndrome , reveal significantly better lipid profile indicators, comparing to WT mice.
Tg mice revealed significantly lower CL , TG , HDL levels compared to WT, while HSP70 in Τg mice significantly increased total SOD activity in red blood cells.
HSP70 also decreased the atherogenic SFAs and increased the anti-atherogenic lipids DIAL, DU, LA, UFA, SM in HDL, nonHDL and in the liver of mice exposed to HFDiets and all Zn concentrations
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Determination of the levels of heavy metals in water, pastures and meat tissues of Pedi goats across two rivers in Limpopo Province, South AfricaManamela, Makwena Precious January 2021 (has links)
Thesis (M. Sc. Agriculture (Animal Production)) -- University of Limpopo, 2021 / The study was carried out to determine the concentration levels of mercury (Hg), lead
(Pb), cadmium (Cd), chromium (Cr), nickel (Ni) and zinc (Zn) in water, soil, witbuffels
grass and meat of goats reared along the river banks of Middle Olifants (Mogalatsana
village) and Mogalakwena (Papegaai village) rivers. The samples were collected from
the river water, soils along the river banks, grass grown along the river banks and male
Pedi goats reared in Mogalatsana and Papegaai villages. The samples were analysed
for the selected heavy metals with an inductively coupled plasma mass spectroscopy
(ICP-MS). Data was analysed as in a complete randomised design. The results of
selected heavy metals in water of both rivers ranged from 0.00 mg/litre of water (Ni
and Cr) to 0.04 mg/litre of water (Hg). The concentration levels of selected heavy
metals in water were similar (P>0.05) for Middle Olifants and Mogalakwena rivers. The
concentration levels of selected heavy metals in the soils along the banks of Middle
Olifants and Mogalakwena rivers ranged from 0.00 mg/kg DM soil (Hg and Cd) to
63.70 mg/kg DM soil (Cr). There were similar (P>0.05) concentration levels of
selected heavy metals in the soils along the banks of Middle Olifants and
Mogalakwena rivers. Heavy metal concentration levels in the witbuffels grass grown
along the banks of Middle Olifants and Mogalakwena rivers ranged from 0.00 mg/kg
DM of grass (Hg and Cd) to 5.05 mg/kg DM of grass (Zn). Similar (P>0.05)
concentrations of selected heavy metals were observed in witbuffels grass grown
along the banks of Middle Olifants and Mogalakwena rivers. However, the
concentration levels of Zn, Pb and Cd in water from both sites were above
internationally maximum permissible levels, indicating that the water from these rivers
was not safe for drinking by humans and animals. The concentration levels of Ni and
Pb in soils from both sites were above internationally recommended maximum
permissible limits. Similarly, chromium concentration levels in witbuffels grass from
both sites were above the recommended maximum permissible limits for livestock,
indicating that the grass was not safe for consumption by livestock. It is recommended
that further studies be conducted to ascertain these findings.
Blood, liver, kidney and meat samples of yearling male Pedi goats grazing along the
banks of Middle Olifants river (Mogalatsana village) had similar (P>0.05) Cr, Cd, Hg,
Ni and Pb concentration levels, respectively. However, goat liver samples had higher
(P<0.05) Zn concentrations than meat, kidney and blood samples. Samples of goat
v
meat contained higher (P<0.05) Zn concentrations than those of kidneys and blood.
Similarly, goat kidney samples contained more (P<0.05) Zn than blood samples.
Blood, liver, kidney and meat samples of Pedi goats grazing along the banks of
Mogalakwena river (Papegaai village) contained similar (P>0.05) concentration levels
of Cr, Cd, Hg, Ni and Pb, respectively. However, goat meat samples contained higher
(P<0.05) Zn concentrations than liver, kidney and blood samples. Samples of goat
liver contained higher (P<0.05) Zn concentration levels than kidney and blood
samples. Similarly, goat kidney samples contained more (P<0.05) Zn than blood
samples.
Meat, blood, liver and kidney samples of male Pedi goats raised in Mogalatsana and
Papegaai villages had similar (P>0.05) chromium, cadmium, mercury, nickel and lead
concentrations, respectively. However, liver and kidney samples of goats from
Mogalatsana village had higher (P<0.05) zinc levels than those from Papegaai village.
Blood and meat samples of goats from Papegaai village had higher (P<0.05) zinc
levels than those from Mogalatsana village. The concentration levels of Zn, Ni, Pb, Cr
and Cd in the blood, liver, kidney and meat samples of male Pedi goats reared along
the banks of Middle Olifants and Mogalakwena rivers were within the maximum
permissible levels for human consumption. Mercury concentration levels in liver,
kidney and meat samples of the goats were within the maximum permissible levels for
human consumption. However, mercury concentration levels in the blood of goats
grazing along the banks of Middle Olifants and Mogalakwena rivers were above the
maximum permissible limit of 0.2 mg/litre of blood. It was concluded that meat, livers
and kidneys of the goats were fit for human consumption. However, blood from these
goats was not fit for human consumption.
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Atmospheric Corrosion of Zn by NaCl, SO2, NH3, O3, and UV LightOnye, Jermain Eze January 2014 (has links)
No description available.
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The effects of micronutrient additions on soil invertebrate activity and community structure along a successional gradientMaloney, Caitlin E. 02 August 2017 (has links)
No description available.
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