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Mitochondrial Calcium in Diabetic Platelets: Friend or Foe?
Başlık:
Mitochondrial Calcium in Diabetic Platelets: Friend or Foe?
Yazar:
Jaji, Zainab Olabisi, author.
ISBN:
9780438132542
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (46 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-11(E), Section: B.
Advisors: John Hwa Committee members: Hyung Chun; Raimund Herzog; Ivana Kuo.
Özet:
The global burden of diabetes mellitus (DM) is projected to keep escalating with a burgeoning of the incidence and prevalence of cardiovascular disease sequalae, which are its major cause of morbidity and mortality. Current antiplatelet therapies used for risk factor reduction have limited efficacy, as such, further investigation into mechanisms provoking platelet dysfunction is warranted. Cytosolic calcium (Ca2+) excess in DM platelets is a well-documented phenomenon in the literature, and various mechanisms have been postulated. However, the ramification of this observation on mitochondrial health has not been explored. We hypothesize that the increase in cytosolic Ca2+ will be absorbed by the mitochondria leading to free mitochondrial matrix Ca2+ surplus and injury. Fluorescent calcium indicators were used to quantify the calcium stores in platelets. Our data indicate that total and free mitochondrial matrix Ca2+ levels were indeed elevated in DM platelets compared to healthy controls. Our findings suggest that the overwhelming oxidative stress environment in DM results in tyrosine-nitration of MICU1 (mitochondrial calcium uptake 1), an activator of MCU (mitochondrial calcium uniporter). Additionally there is a 30% reduction in the negative MCU regulator, MICU2. Combined, the excess entry of cytosolic calcium likely contributes to the observed mitochondrial damage and dysfunction observed with DM platelets. Restoring platelet calcium handling to homeostasis may alleviate platelet hyperactivity in DM.
Notlar:
School code: 0265
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
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