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Inflammation and ap...
Inflammation and apoptosis in aortic tissues of aged type II diabetes : Amelioration with alpha-lipoic acid through phosphatidylinositol 3-kinase/Akt- dependent mechanism
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Bitar, Milad S. (author)
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Ayed, Adel K. (author)
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- Abdel-Halim, Samy M. (author)
- Uppsala universitet,Lungmedicin och allergologi
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Isenovic, Esma R. (author)
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Al-Mulla, Fahd (author)
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(creator_code:org_t)
- Elsevier BV, 2010
- 2010
- English.
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In: Life Sciences. - : Elsevier BV. - 0024-3205 .- 1879-0631. ; 86:23-24, s. 844-853
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Aims: Endothelial dysfunction is a key triggering event in the development of cardiovascular diseases and the current study explored this phenomenon in the context of inflammation, apoptosis, reactive oxygen species (ROS) and the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway during chronic diabetes. Main methods: alpha-Lipoic acid (ALA) and wortmannin (WM) were chronically administered to aged Goto Kakizaki (GK) rats, a genetic model of non-obese type II diabetes. Key indices of inflammation, apoptosis and oxidative stress were assessed using western blotting, real-time PCR and immunofluoresence-based techniques. Key findings: A chronic inflammation (e.g., increased mRNA/protein levels of INF-alpha, ICAM, fractalkine, CD-68, myeloperoxidase) in connection with increased caspase-based apoptotic cell death and heightened state of oxidative stress (HSOS)- appear to exist in diabetic cardiovascular tissues. An assessment of NF-kappa B dynamics in aged diabetic vessels revealed not only a marked increase in cytosolic phosphorylated levels of I kappa B-alpha, NIK, IRK but also an enhancement in nuclear localization of p65 concomitantly with augmented NF-kappa B-DNA binding activity. Most of the aforementioned cardiovascular-based diabetic abnormalities including reduced activities of PI3K and Akt kinase were ameliorated following chronic ALA therapy. WM, given to GK rats negated the anti-inflammatory and anti-apoptotic actions of ALA. Significance: Our data highlight a unifying mechanism whereby HSOS through an induction of NF-kappa B activity together with an impairment in PI3K/Akt pathway favors pro-inflammatory/pro-apoptotic diabetic vascular milieu that culminate in the onset of endothelial dysfunction, a phenomenon which appears to be amenable to treatment with antioxidants and/or PI3/Akt mimetics (e.g., ALA).
Keyword
- Diabetes
- Inflammation
- Apoptosis
- Oxidative stress
- alpha-lipoic acid
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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