Two sodium/calcium exchanger gene products, NCX1 and NCX3, play a major role in the development of permanent focal cerebral ischemia.
نویسندگان
چکیده
BACKGROUND AND PURPOSE The Na+/Ca2+ exchanger, by mediating Ca2+ and Na+ fluxes in a bidirectional way across the synaptic plasma membrane, may play a pivotal role in the events leading to anoxic damage. In the brain, there are 3 different genes coding for 3 different proteins: NCX1, NCX2, and NCX3. The aim of this study was to determine whether NCX1, NCX2, and NCX3 might play a differential role in the development of cerebral injury induced by permanent middle cerebral artery occlusion (pMCAO). METHODS By means of Western blotting, NCX1, NCX2, and NCX3 protein expression was evaluated in the ischemic core and in the remaining nonischemic area of the slice at different time intervals starting from ischemia induction. The role of each isoform was also assessed with antisense oligodeoxynucleotides (ODNs) targeted for each isoform. These ODNs were continuously intracerebroventricularly infused with an osmotic minipump (1 microL/h) for 48 hours, 24 hours before pMCAO. RESULTS The results showed that after pMCAO all 3 NCX proteins were downregulated in ischemic core; NCX3 decreased in periinfarctual area whereas NCX1 and NCX2 were unchanged. The ODNs for NCX1 and NCX3 gene products were capable of inducing an increase in the ischemic lesion and to worsen neurological scores. CONCLUSIONS The results of this study suggest that in the neuroprotective effect exerted by NCX during ischemic injury, the major role is prevalently exerted by NCX1 and NCX3 gene products.
منابع مشابه
Protective Effect of the Viola Spathulata Extract on NCX3 Gene Expression in an Animal Model of Cerebral Ischemia
Abstract_ Introduction: Viola plant has been used traditionally for the treatment of neurological disorders. We aimed at determining whether pretreatment with Viola spathulata extract can alleviate the severity of ischemic-reperfusion damages and it can exert its protective effects through the regulation of a sodium/calcium exchanger (NCX3) gene expression in a rat brain. Methods: Male Wistar r...
متن کاملNCX1 expression and functional activity increase in microglia invading the infarct core.
BACKGROUND AND PURPOSE The sodium-calcium exchanger NCX1 represents a key mediator for maintaining [Na(+)](i) and [Ca(2+)](i) in anoxic conditions. To date, no information is available on NCX1 protein expression and activity in microglial cells under ischemic conditions. METHODS By means of Western blotting, patch-clamp electrophysiology, single-cell Fura-2 acetoxymethyl-ester microfluorometr...
متن کاملBHK cells transfected with NCX3 are more resistant to hypoxia followed by reoxygenation than those transfected with NCX1 and NCX2: Possible relationship with mitochondrial membrane potential.
The specific role played by NCX1, NCX2, and NCX3, the three isoforms of the Na+/Ca2+ exchanger (NCX), has been explored during hypoxic conditions in BHK cells stably transfected with each of these isoforms. Six major findings emerged from the present study: (1) all the three isoforms were highly expressed on the plasma membranes of BHK cells; (2) under physiological conditions, the three NCX is...
متن کاملTargeted disruption of Na+/Ca2+ exchanger 3 (NCX3) gene leads to a worsening of ischemic brain damage.
Na+/Ca+ exchanger 3 (NCX3), one of the three isoforms of the NCX family, is highly expressed in the brain and is involved in the maintenance of intracellular Na+ and Ca2+ homeostasis. Interestingly, whereas the function of NCX3 under physiological conditions has been determined, its role under anoxia is still unknown. To assess NCX3 role in cerebral ischemia, we exposed ncx3-/- mice to transien...
متن کاملAnoxia-Induced NF-kB-Dependent Upregulation of NCX1 Contributes to Ca Refilling Into Endoplasmic Reticulum in Cortical Neurons
Background and Purpose—The 3 gene products of the Na /Ca exchanger (NCX), viz, NCX1, NCX2, and NCX3, may play a pivotal role in the pathophysiology of brain ischemia. The aim of this study was to investigate the transductional and posttranslational mechanisms involved in the expression of these isoforms during oxygen and glucose deprivation and their role in endoplasmic reticulum Ca refilling i...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Stroke
دوره 35 11 شماره
صفحات -
تاریخ انتشار 2004