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Acute and subchronic exposure to air particulate matter induces expression of angiotensin and bradykinin-related genes in the lungs and heart: Angiotensin-II type-I receptor as a molecular target of particulate matter exposure.

Aztatzi-Aguilar OG, Uribe-Ramírez M, Arias-Montaño JA, Barbier O, De Vizcaya-Ruiz A - Part Fibre Toxicol (2015)

Bottom Line: The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner.The AT1R lung protein showed a time-dependent change in subcellular distribution.In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional, 2508, México D. F, CP. 07360, Mexico. gammaztatzi@gmail.com.

ABSTRACT

Background: Particulate matter (PM) adverse effects on health include lung and heart damage. The renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) endocrine systems are involved in the pathophysiology of cardiovascular diseases and have been found to impact lung diseases. The aim of the present study was to evaluate whether PM exposure regulates elements of RAAS and KKS.

Methods: Sprague-Dawley rats were acutely (3 days) and subchronically (8 weeks) exposed to coarse (CP), fine (FP) or ultrafine (UFP) particulates using a particulate concentrator, and a control group exposed to filtered air (FA). We evaluated the mRNA of the RAAS components At1, At2r and Ace, and of the KKS components B1r, B2r and Klk-1 by RT-PCR in the lungs and heart. The ACE and AT1R protein were evaluated by Western blot, as were HO-1 and γGCSc as indicators of the antioxidant response and IL-6 levels as an inflammation marker. We performed a binding assay to determinate AT1R density in the lung, also the subcellular AT1R distribution in the lungs was evaluated. Finally, we performed a histological analysis of intramyocardial coronary arteries and the expression of markers of heart gene reprogramming (Acta1 and Col3a1).

Results: The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner. CP exposure induced Ace mRNA expression and regulated its protein in the lungs. Acute and subchronic exposure to FP and UFP induced the expression of At1r in the lungs and heart. All PM fractions increased the AT1R protein in a size-dependent manner in the lungs and heart after subchronic exposure. The AT1R lung protein showed a time-dependent change in subcellular distribution. In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6. Moreover, exposure to all PM fractions increased coronary artery wall thickness.

Conclusion: We demonstrate that exposure to PM induces the expression of RAAS and KKS elements, including AT1R, which was the main target in the lungs and the heart.

No MeSH data available.


Related in: MedlinePlus

Particle matter modifies the AT1R subcellular distribution in lung tissue in a time-dependent manner. Representative gels of Angiotensin-II type-I receptor (AT1R) detection in lung nuclear and non-nuclear fractions after acute (upper panel) and subchronic (lower panel) exposure to coarse particulate (CP), fine particulate (FP), ultrafine particulate (UFP) or filtered air (AF). We used GAPDH and acetylated Histone-4 (H4ac) as cytosolic and nuclear quality control targets, respectively, and actin was used as a general protein loading control. Representative blot of n = 4
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Fig4: Particle matter modifies the AT1R subcellular distribution in lung tissue in a time-dependent manner. Representative gels of Angiotensin-II type-I receptor (AT1R) detection in lung nuclear and non-nuclear fractions after acute (upper panel) and subchronic (lower panel) exposure to coarse particulate (CP), fine particulate (FP), ultrafine particulate (UFP) or filtered air (AF). We used GAPDH and acetylated Histone-4 (H4ac) as cytosolic and nuclear quality control targets, respectively, and actin was used as a general protein loading control. Representative blot of n = 4

Mentions: The conventional paradigm for GPCRs indicates that the activated receptors are internalized from the plasma membrane to the cytoplasm where they may be degraded or recycled [47]. However, new evidence indicates that some GPCRs can be localized in the nuclear envelope [48]. In the case of AT1R, Lu et al. reported that after 15 min of stimulation of neuronal cell cultures with Ang-II, AT1R was sequestered to the nuclear membrane [49]. However, Tadevosyan et al. [50] demonstrated that the presence of angiotensin receptors (AT1R and AT2R) in the nuclear membrane is most likely a result of intracellular synthesis and trafficking, and not the result of post-endocytotic trafficking in cardiomyocyte cultures. For these reasons, we evaluated the distribution of AT1R protein between the nuclei and the rest of the cell in the lung tissue following exposure to airborne PM in both exposure schemes (Fig. 4). For the acute exposures, we observed an increase in AT1R in the non-nuclear fraction in all exposed groups, while in the nuclear fraction we observed a reduction in protein levels (Fig. 4, upper panel). On the other hand, following the subchronic exposures, we observed the opposite response: under these conditions, we observed a decrease in AT1R levels in the non-nuclear fraction and an increase in this protein in the nuclear fraction (Fig. 4, lower panel).Fig. 4


Acute and subchronic exposure to air particulate matter induces expression of angiotensin and bradykinin-related genes in the lungs and heart: Angiotensin-II type-I receptor as a molecular target of particulate matter exposure.

Aztatzi-Aguilar OG, Uribe-Ramírez M, Arias-Montaño JA, Barbier O, De Vizcaya-Ruiz A - Part Fibre Toxicol (2015)

Particle matter modifies the AT1R subcellular distribution in lung tissue in a time-dependent manner. Representative gels of Angiotensin-II type-I receptor (AT1R) detection in lung nuclear and non-nuclear fractions after acute (upper panel) and subchronic (lower panel) exposure to coarse particulate (CP), fine particulate (FP), ultrafine particulate (UFP) or filtered air (AF). We used GAPDH and acetylated Histone-4 (H4ac) as cytosolic and nuclear quality control targets, respectively, and actin was used as a general protein loading control. Representative blot of n = 4
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4482198&req=5

Fig4: Particle matter modifies the AT1R subcellular distribution in lung tissue in a time-dependent manner. Representative gels of Angiotensin-II type-I receptor (AT1R) detection in lung nuclear and non-nuclear fractions after acute (upper panel) and subchronic (lower panel) exposure to coarse particulate (CP), fine particulate (FP), ultrafine particulate (UFP) or filtered air (AF). We used GAPDH and acetylated Histone-4 (H4ac) as cytosolic and nuclear quality control targets, respectively, and actin was used as a general protein loading control. Representative blot of n = 4
Mentions: The conventional paradigm for GPCRs indicates that the activated receptors are internalized from the plasma membrane to the cytoplasm where they may be degraded or recycled [47]. However, new evidence indicates that some GPCRs can be localized in the nuclear envelope [48]. In the case of AT1R, Lu et al. reported that after 15 min of stimulation of neuronal cell cultures with Ang-II, AT1R was sequestered to the nuclear membrane [49]. However, Tadevosyan et al. [50] demonstrated that the presence of angiotensin receptors (AT1R and AT2R) in the nuclear membrane is most likely a result of intracellular synthesis and trafficking, and not the result of post-endocytotic trafficking in cardiomyocyte cultures. For these reasons, we evaluated the distribution of AT1R protein between the nuclei and the rest of the cell in the lung tissue following exposure to airborne PM in both exposure schemes (Fig. 4). For the acute exposures, we observed an increase in AT1R in the non-nuclear fraction in all exposed groups, while in the nuclear fraction we observed a reduction in protein levels (Fig. 4, upper panel). On the other hand, following the subchronic exposures, we observed the opposite response: under these conditions, we observed a decrease in AT1R levels in the non-nuclear fraction and an increase in this protein in the nuclear fraction (Fig. 4, lower panel).Fig. 4

Bottom Line: The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner.The AT1R lung protein showed a time-dependent change in subcellular distribution.In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6.

View Article: PubMed Central - PubMed

Affiliation: Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional, 2508, México D. F, CP. 07360, Mexico. gammaztatzi@gmail.com.

ABSTRACT

Background: Particulate matter (PM) adverse effects on health include lung and heart damage. The renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) endocrine systems are involved in the pathophysiology of cardiovascular diseases and have been found to impact lung diseases. The aim of the present study was to evaluate whether PM exposure regulates elements of RAAS and KKS.

Methods: Sprague-Dawley rats were acutely (3 days) and subchronically (8 weeks) exposed to coarse (CP), fine (FP) or ultrafine (UFP) particulates using a particulate concentrator, and a control group exposed to filtered air (FA). We evaluated the mRNA of the RAAS components At1, At2r and Ace, and of the KKS components B1r, B2r and Klk-1 by RT-PCR in the lungs and heart. The ACE and AT1R protein were evaluated by Western blot, as were HO-1 and γGCSc as indicators of the antioxidant response and IL-6 levels as an inflammation marker. We performed a binding assay to determinate AT1R density in the lung, also the subcellular AT1R distribution in the lungs was evaluated. Finally, we performed a histological analysis of intramyocardial coronary arteries and the expression of markers of heart gene reprogramming (Acta1 and Col3a1).

Results: The PM fractions induced the expression of RAAS and KKS elements in the lungs and heart in a time-dependent manner. CP exposure induced Ace mRNA expression and regulated its protein in the lungs. Acute and subchronic exposure to FP and UFP induced the expression of At1r in the lungs and heart. All PM fractions increased the AT1R protein in a size-dependent manner in the lungs and heart after subchronic exposure. The AT1R lung protein showed a time-dependent change in subcellular distribution. In addition, the presence of AT1R in the heart was accompanied by a decrease in HO-1, which was concomitant with the induction of Acta1 and Col3a1 and the increment of IL-6. Moreover, exposure to all PM fractions increased coronary artery wall thickness.

Conclusion: We demonstrate that exposure to PM induces the expression of RAAS and KKS elements, including AT1R, which was the main target in the lungs and the heart.

No MeSH data available.


Related in: MedlinePlus