Limits...
Cellular stress response, sirtuins and UCP proteins in Alzheimer disease: role of vitagenes.

Cornelius C, Trovato Salinaro A, Scuto M, Fronte V, Cambria MT, Pennisi M, Bella R, Milone P, Graziano A, Crupi R, Cuzzocrea S, Pennisi G, Calabrese V - Immun Ageing (2013)

Bottom Line: Vitagenes encode for cytoprotective heat shock proteins (Hsp), as well as thioredoxin, sirtuins and uncouple proteins (UCPs).In the present study we evaluate stress response mechanisms in plasma and lymphocytes of AD patients, as compared to controls, in order to provide evidence of an imbalance of oxidant/antioxidant mechanisms and oxidative damage in AD patients and the possible protective role of vitagenes.We found that the levels of Sirt-1 and Sirt-2 in AD lymphocytes were significantly higher than in control subjects.Interestingly, analysis of plasma showed in AD patients increased expression of Trx, a finding associated with reduced expression of UCP1, as compared to control group.This finding can open up new neuroprotective strategies, as molecules inducing this defense mechanisms can represent a therapeutic target to minimize the deleterious consequences associated to oxidative stress, such as in brain aging and neurodegenerative disorders.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Sciences, University of Catania, Catania, Italy. calabres@unict.it.

ABSTRACT
Alzheimer's Disease (AD) is a neurodegenerative disorder affecting up to one third of individuals reaching the age of 80. Different integrated responses exist in the brain to detect oxidative stress which is controlled by several genes termed Vitagenes. Vitagenes encode for cytoprotective heat shock proteins (Hsp), as well as thioredoxin, sirtuins and uncouple proteins (UCPs). In the present study we evaluate stress response mechanisms in plasma and lymphocytes of AD patients, as compared to controls, in order to provide evidence of an imbalance of oxidant/antioxidant mechanisms and oxidative damage in AD patients and the possible protective role of vitagenes.We found that the levels of Sirt-1 and Sirt-2 in AD lymphocytes were significantly higher than in control subjects. Interestingly, analysis of plasma showed in AD patients increased expression of Trx, a finding associated with reduced expression of UCP1, as compared to control group.This finding can open up new neuroprotective strategies, as molecules inducing this defense mechanisms can represent a therapeutic target to minimize the deleterious consequences associated to oxidative stress, such as in brain aging and neurodegenerative disorders.

No MeSH data available.


Related in: MedlinePlus

Thioredoxin (Trx) protein levels in lymphocytes of AD and control subjects. Samples from control and AD subjects were assayed for Trx expression by Western blot. A) Densitometric evaluation: the bar graph shows the values are expressed as mean standard error of mean of 3 independent analyses. P ≤ 0.05 vs control. B) A representative immunoblot is shown. β-actin has been used as loading control. D.U., densitometric units; AD, Alzheimer’s disease; CTRL, control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3842652&req=5

Figure 4: Thioredoxin (Trx) protein levels in lymphocytes of AD and control subjects. Samples from control and AD subjects were assayed for Trx expression by Western blot. A) Densitometric evaluation: the bar graph shows the values are expressed as mean standard error of mean of 3 independent analyses. P ≤ 0.05 vs control. B) A representative immunoblot is shown. β-actin has been used as loading control. D.U., densitometric units; AD, Alzheimer’s disease; CTRL, control.

Mentions: Alzheimer’s disease (AD) is the most common form of dementia and is characterized pathologically by senile plaques, neurofibrillary tangles and cerebral amyloid angiopathy[30-32]. Figure 1 reports brain MRI axial T2 image showing cerebral atrophy in patient with Alzheimer’s disease in comparison to a normal brain. Our laboratory previously demonstrated in the brain as well as in peripheral blood that oxidative and nitrosative stress occur in AD patients, compared to normal subjects[33] and that this can serve as a trigger for induction of the heat shock response[18,34,35]. Therefore, we evaluated the expression levels of Trx and Sirtuin in the plasma and lymphocytes in control and in AD patients. Western blot analysis of lymphocytes probed for Sirt-1 is reported in Figure 2. Sirt-1 expression is significantly increased in AD patients, compared to controls. In contrast to Sirt-1, expression levels of Sirt-2 measured in lymphocytes did not show a significant increase in AD patients compared to controls (Figure 3). As shown in Figure 4, analysis of lymphocytes in AD patients, compared to control group, revealed also an increase in thioredoxin protein expression. Consistently to the observed changes in AD lymphocytes, analysis of plasma in AD patients showed higher expression levels of Sirt-1 (Figure 5). Expression levels of Sirt-2 were also measured and results, reported in Figure 6, show an increase in AD patients, which however was not statistically significant, as compared to control group. As far as we are concerned, this is the first evidence demonstrating changes in SIRT-1 expression in AD, although at the moment we cannot exclude that this might not be a specific alteration of this progressive inflammatory neurodegenerative disease associated with oxidative stress which has emerged as a critical factor in AD. Interestingly, we investigated the expression of Trx and we found, in the plasma, higher levels of Trx protein in AD patients compared with the control group (Figure 7). Figure 8 shows a decreased expression of UCP1 protein in plasma of AD patients compared to controls. Analysis of lymphocytes in AD patients, compared to control group, did not allow to detect measurable levels of this protein (data not shown).


Cellular stress response, sirtuins and UCP proteins in Alzheimer disease: role of vitagenes.

Cornelius C, Trovato Salinaro A, Scuto M, Fronte V, Cambria MT, Pennisi M, Bella R, Milone P, Graziano A, Crupi R, Cuzzocrea S, Pennisi G, Calabrese V - Immun Ageing (2013)

Thioredoxin (Trx) protein levels in lymphocytes of AD and control subjects. Samples from control and AD subjects were assayed for Trx expression by Western blot. A) Densitometric evaluation: the bar graph shows the values are expressed as mean standard error of mean of 3 independent analyses. P ≤ 0.05 vs control. B) A representative immunoblot is shown. β-actin has been used as loading control. D.U., densitometric units; AD, Alzheimer’s disease; CTRL, control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842652&req=5

Figure 4: Thioredoxin (Trx) protein levels in lymphocytes of AD and control subjects. Samples from control and AD subjects were assayed for Trx expression by Western blot. A) Densitometric evaluation: the bar graph shows the values are expressed as mean standard error of mean of 3 independent analyses. P ≤ 0.05 vs control. B) A representative immunoblot is shown. β-actin has been used as loading control. D.U., densitometric units; AD, Alzheimer’s disease; CTRL, control.
Mentions: Alzheimer’s disease (AD) is the most common form of dementia and is characterized pathologically by senile plaques, neurofibrillary tangles and cerebral amyloid angiopathy[30-32]. Figure 1 reports brain MRI axial T2 image showing cerebral atrophy in patient with Alzheimer’s disease in comparison to a normal brain. Our laboratory previously demonstrated in the brain as well as in peripheral blood that oxidative and nitrosative stress occur in AD patients, compared to normal subjects[33] and that this can serve as a trigger for induction of the heat shock response[18,34,35]. Therefore, we evaluated the expression levels of Trx and Sirtuin in the plasma and lymphocytes in control and in AD patients. Western blot analysis of lymphocytes probed for Sirt-1 is reported in Figure 2. Sirt-1 expression is significantly increased in AD patients, compared to controls. In contrast to Sirt-1, expression levels of Sirt-2 measured in lymphocytes did not show a significant increase in AD patients compared to controls (Figure 3). As shown in Figure 4, analysis of lymphocytes in AD patients, compared to control group, revealed also an increase in thioredoxin protein expression. Consistently to the observed changes in AD lymphocytes, analysis of plasma in AD patients showed higher expression levels of Sirt-1 (Figure 5). Expression levels of Sirt-2 were also measured and results, reported in Figure 6, show an increase in AD patients, which however was not statistically significant, as compared to control group. As far as we are concerned, this is the first evidence demonstrating changes in SIRT-1 expression in AD, although at the moment we cannot exclude that this might not be a specific alteration of this progressive inflammatory neurodegenerative disease associated with oxidative stress which has emerged as a critical factor in AD. Interestingly, we investigated the expression of Trx and we found, in the plasma, higher levels of Trx protein in AD patients compared with the control group (Figure 7). Figure 8 shows a decreased expression of UCP1 protein in plasma of AD patients compared to controls. Analysis of lymphocytes in AD patients, compared to control group, did not allow to detect measurable levels of this protein (data not shown).

Bottom Line: Vitagenes encode for cytoprotective heat shock proteins (Hsp), as well as thioredoxin, sirtuins and uncouple proteins (UCPs).In the present study we evaluate stress response mechanisms in plasma and lymphocytes of AD patients, as compared to controls, in order to provide evidence of an imbalance of oxidant/antioxidant mechanisms and oxidative damage in AD patients and the possible protective role of vitagenes.We found that the levels of Sirt-1 and Sirt-2 in AD lymphocytes were significantly higher than in control subjects.Interestingly, analysis of plasma showed in AD patients increased expression of Trx, a finding associated with reduced expression of UCP1, as compared to control group.This finding can open up new neuroprotective strategies, as molecules inducing this defense mechanisms can represent a therapeutic target to minimize the deleterious consequences associated to oxidative stress, such as in brain aging and neurodegenerative disorders.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Biomedical Sciences, University of Catania, Catania, Italy. calabres@unict.it.

ABSTRACT
Alzheimer's Disease (AD) is a neurodegenerative disorder affecting up to one third of individuals reaching the age of 80. Different integrated responses exist in the brain to detect oxidative stress which is controlled by several genes termed Vitagenes. Vitagenes encode for cytoprotective heat shock proteins (Hsp), as well as thioredoxin, sirtuins and uncouple proteins (UCPs). In the present study we evaluate stress response mechanisms in plasma and lymphocytes of AD patients, as compared to controls, in order to provide evidence of an imbalance of oxidant/antioxidant mechanisms and oxidative damage in AD patients and the possible protective role of vitagenes.We found that the levels of Sirt-1 and Sirt-2 in AD lymphocytes were significantly higher than in control subjects. Interestingly, analysis of plasma showed in AD patients increased expression of Trx, a finding associated with reduced expression of UCP1, as compared to control group.This finding can open up new neuroprotective strategies, as molecules inducing this defense mechanisms can represent a therapeutic target to minimize the deleterious consequences associated to oxidative stress, such as in brain aging and neurodegenerative disorders.

No MeSH data available.


Related in: MedlinePlus