Role of uroguanylin's signalling pathway in the development of ischaemic stroke (CROSBI ID 309356)
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Podaci o odgovornosti
Ratko, Martina ; Habek, Nikola ; Dobrivojević Radmilović, Marina ; Škokić, Siniša ; Justić, Helena ; Barić, Anja ; Dugandžić, Aleksandra
engleski
Role of uroguanylin's signalling pathway in the development of ischaemic stroke
Stroke is one of the leading causes of mortality and disability worldwide. By affecting bradykinin function, activation of guanylate cyclase (GC)-A has been shown to have a neuroprotective effect after ischaemic stroke, whereas the same has not been confirmed for GC-B ; therefore, we aimed to determine the possible role of GC-C and its agonist, uroguanylin (UGN), in the development of stroke. In this study, middle cerebral artery occlusion (MCAO) was performed on wild-type (WT), GC-C KO and UGN KO mice. MR images were acquired before and 24 h after MCAO. On brain slices 48 h after MCAO, the Ca2+ response to UGN stimulation was recorded. Our results showed that the absence of GC-C in GC-C KO mice resulted in the development of smaller ischaemic lesions compared with WT littermates, which is an opposite effect compared with the effects of GC-A agonists on brain lesions. WT and UGN KO animals showed a stronger Ca2+ response upon UGN stimulation in astrocytes of the peri-ischaemic cerebral cortex compared with the same cortical region of the unaffected contralateral hemisphere. This stronger activation was not observed in GC-C KO animals, which may be the reason for smaller lesion development in GC-C KO mice. The reason why GC-C might affect Ca2+ signalling in peri-ischaemic astrocytes is that GC-C is expressed in these cells after MCAO, whereas under normoxic conditions, it is expressed mainly in cortical neurons. Stronger activation of the Ca2+ - dependent signalling pathway could lead to the stronger activation of the Na+ /H+ exchanger, tissue acidification and neuronal death.
Ca2+ signalling ; GC-C knockout animals ; UGN knockout animals ; astrocytes ; guanylate cyclase C.
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Podaci o izdanju
56 (1)
2022.
3720-3737
objavljeno
0953-816X
1460-9568
10.1111/ejn.15674
Povezanost rada
Temeljne medicinske znanosti