Evaluation of Sirtuin Role in Neuroprotection of Retinal Ganglion Cells in Hypoxia

Effects of Semaphorin 3A on Retinal Pigment Epithelial Cell Activity

“…CoCl 2 is a chemical hypoxic agent, which can induce the secretion of endogenous VEGF 165 as reported. 24,25 As shown in Figure 7, in CoCl 2 -treated groups, Sema3A showed no effect on VEGF 165 and PEDF secretion (compared with the CoCl 2 -treated group), however, Sema3A inhibited endogenous free VEGF 165 utilization ability (Fig. 7).…”

“…24,25 Sema3A (250 ng/mL and 500 ng/mL) was incubated with RPE in 96-well plates for 24, 48, and 72 hours with or without CoCl 2 . At indicated time-points, the cell culture supernatant were collected to measure VEGF 165 and PEDF concentration.…”

Localization of sirtuins in the mouse inner ear

“…SIRT1 preserves retinal ganglion cells during hypoxia. The neuroprotective effect of SIRT1 requires interaction with apoptotic signaling proteins so as to reduce or prevent hypoxia-induced apoptosis [8,9]. In the inner ear, SIRT1 was found in type I and V fibrocytes in the SL, in vestibular dark cells and in endolymphatic sac epithelial cells, suggesting a relationship with ion and water transport in the inner ear.…”

WISP1: Clinical Insights for a Proliferative and Restorative Member of the CCN Family

“…Of the seven mammalian homologues of Sir2 that include SIRT1 through SIRT7, SIRT1 plays a significant role in oxidative stress, cell metabolism, genomic stability, cell survival, neurodegenerative disease, infection, and cardiovascular disease [102–107]. In regards to cytoprotection, SIRT1 activation can prevent hypoxic injury in retinal ganglion cells [108], modulate cell longevity [109, 110], protect against high-fat diet-induced metabolic abnormalities [111, 112], increase cellular survival during anoxia and ischemia [113, 114], reduce Aβ toxicity [115], reverse impaired fat and glucose metabolism [12, 116–118], maintain mitochondrial processing and quality through autophagy [119], foster cellular protection against radiation [120], protect against renal cell aging [121], block apoptotic pathways in preadipocytes [122], and modulate forkhead mediated apoptotic pathways [53, 72, 96, 118, 123–126]. Yet, other studies suggest that to achieve cytoprotection through sirtuin pathways, the level of sirtuin activity may be critical [53, 72, 115, 127], since SIRT1 gene polymorphisms may affect protein expression during cardiovascular disease [105], SIRT1 activity can promote tumor growth [128, 129], and reduction in SIRT1 activity has been reported to enhance the cytoprotective effects of IGF-1 [130].…”

“…Loss of sirtuin activity can be a result of the nuclear degradation of the sirtuin SIRT1 [127] and lead to the subsequent activation of caspases [108, 127]. SIRT1 degradation may be mediated by apoptotic pathways linked to p38 [169] and JNK1 [170].…”