Heat shock protein 72 confers protection in retinal ganglion cells and lateral geniculate nucleus neurons via blockade of the SAPK/JNK pathway in a chronic ocular-hypertensive rat model

Abstract

Optic nerve transection increased the expression of heat shock protein 72 (HSP72) in the lateral geniculate body, indicating that this protein is involved in the prevention of neuronal injury. Zinc sulfate and quercetin induced and inhibited the expression of HSP72, respectively. Intraperitoneal injections of zinc sulfate, SP600125 (c-Jun N-terminal kinase inhibitor), or quercetin were performed on retinal ganglion cells in a Wistar rat model of chronic ocular hypertension. Our results showed that compared with the control group, the expression of HSP72 in retinal ganglion cells and the lateral geniculate body was increased after the injection of zinc sulfate, but was decreased after the injection of quercetin. The expression of phosphorylated c-Jun N-terminal kinases and phosphorylated c-Jun were visible 3 days after injection in the control group, and reached a peak at 7 days. Zinc sulfate and SP600125 significantly decreased the expression of p-c-Jun, whereas quercetin significantly enhanced the expression of this protein. These results suggest that HSP72 protects retinal ganglion cells and lateral geniculate body in a rat model of chronic ocular hypertension from injury by blocking the activation of the stress-activated kinase/c-Jun N-terminal kinase apoptotic pathway.

Heat shock proteins in the retina: Focus on HSP70 and alpha crystallins in ganglion cell survival

“…The involvement of HSP70 in RGC protection was further demonstrated in animals injected with quercetin, which diminished the HSP70 expression and significantly decreased the number of surviving RGCs in the zinc-treated group (Park et al, 2001b). Zinc sulfate-induced upregulation of HSP72 was associated with blockage of the stress-activated protein kinase SAPK/JNK apoptotic pathway, and consequently with enhanced RGC and lateral geniculate nucleus neuron survival in rat glaucoma model (Li et al, 2014). …”

Evaluation of heat shock protein (HSP-72) expression in retinal ganglion cells of rats with glaucoma

“…The molecular weight of inducible HSP72 is 72 kDa, so it is also known as HSP72, with low expression level in non-stress state, but the expression level would markedly increase in stress state to protect during injury or repair ( 4 , 12 , 13 ). It has been shown ( 14 ) that HSP72 could protect neural pathways by interdicting the activity of apoptosis pathway SAPK/JNK in RGCs and lateral geniculate body nerve cells ( 5 ). HSP72 is considered as an apoptosis inhibitor.…”

Mitochondrial Dysfunction as a Novel Target for Neuroprotective Nutraceuticals in Ocular Diseases

“…Zhou and colleagues recently report quercetin alleviates the excitability of RGCs through increased miniature GABAergic neurotransmission and decreasing miniature glutamatergic neurotransmission [ 94 ]. On the other hand, some studies have demonstrated that quercetin has an inhibitory effect of heat shock protein 72 (HSP 72) in RGCs [ 95 , 96 , 97 ]. Quercetin has neuroprotective effects of retinal layers [ 98 ] and cytoprotective effects of photoreceptor, RPE and RGCs through inhibiting activity of AP-1 pathway [ 99 ] in light-induced retinal degeneration rodent models.…”