Deletion of the ageing gene p66Shc reduces early stroke size following ischaemia/reperfusion brain injury

Abstract

In the present study, we show that the deletion of the ageing gene p66(Shc) protects mice from ischaemia/reperfusion brain injury through a blunted production of free radicals. The ROS mediator p66(Shc) may represent a novel therapeutical target for the treatment of ischaemic stroke.

Activated protein C ameliorates diabetic nephropathy by epigenetically inhibiting the redox enzyme p66 Shc

“…p66 Shc has been linked not only to diabetic nephropathy, but also to various other conditions, such as other glomerulopathies, cardiomyopathy, ischemia/reperfusion injury, neurodegenerative diseases, and in vitro models of intestinal cell dysfunction (27)(28)(29)(30). Likewise, aPC has evolved as a panacea, ameliorating a broad array of experimental diseases, including experimental cardiac or renal ischemia reperfusion injury, neurodegenerative diseases, inflammatory bowel disease, and diabetic glomerulopathy (1,31).…”

Adaptor Protein p66 Shc Mediates Hypertension-Associated, Cyclic Stretch–Dependent, Endothelial Damage

“…Shc belongs to the mammalian Shc adaptor protein family, 13,14 participates in ROS production, [15][16][17][18][19] and is involved in translation of oxidative stimuli into apoptosis. 20,21 Genetic deletion of p66 Shc in mice was shown to improve endothelial function in different disease models.…”

Chronic nicotine exposure augments renal oxidative stress and injury through transcriptional activation of p66shc

“…Moreover, substitution of Ser36 for the phosphomimetic aspartic acid (S36D) did not attenuate Ch-NIC-induced adverse effects, suggesting that serine phosphorylation of the Ser36 residue of p66shc is essential for mediating the adverse effects of Ch-NIC. The role of Ser36-phosphorylated p66shc is widely recognized in the pathogenesis of a variety of diseases including but not restricted to cardiovascular diseases [39], type 2 diabetes [40], impaired mitogenic signaling in T cells [41] and stroke [42]. Also, the role of p66shc in smoking-associated increase in cardiovascular oxidative stress is proposed [39] but has never been studied.…”