Abstract
Prolonged hyperglycemia-induced oxidative stress and endoplasmic reticulum stress have been demonstrated to play a key role in progression of diabetic peripheral neuropathy (DPN). PERK/ Nrf2 pathway plays a predominant role in oxidative and endoplasmic reticulum (ER) stress which is associated with cell survival. This study examined the modulation of the PERK/Nrf2 pathway and apoptosis by a traditional Chinese medicine Tangluoning (TLN) in streptozotocin-induced DPN rat models and the effects of serum TLN on the PERK/Nrf2 pathway, apoptosis, intracellular reactive oxygen species and mitochondrial membrane potential in Schwann cells cultured in 150 mM glucose. It is found that TLN attenuated oxidative and ER stress and apoptosis through the PERK/Nrf2 pathway by upregulating p-PERK, Nrf2/ARE pathways and downregulating the CHOP-related apoptosis pathways in the experimental DPN models both in vivo and in vitro.
Highlights
Diabetic peripheral neuropathy (DPN) is characterized by high morbidity and premature mortality
An upregulation of the endoplasmic reticulum (ER) chaperone glucose-regulated protein 78 (GRP78) was detected in the diabetic peripheral neuropathy (DPN) rats using western blot analysis compared to normal rats, which was further increased in TLN-treated rats (Fig. 1B)
These results demonstrate that TLN might play a protective role in oxidative stress in the DPN rats by up-regulating the PERK/Nrf[2] signaling pathways
Summary
Diabetic peripheral neuropathy (DPN) is characterized by high morbidity and premature mortality. The pathogenesis of DPN results in a widespread damage to all components of peripheral nervous system (PNS) such as dorsal rout ganglia, neurons, vasa nervorum, and primarily, the Schwann cells[3]. Chronic hyperglycemia induces both oxidative stress and endoplasmic reticulum (ER) stress, which are two key factors leading to neuronal apoptosis[4, 5], and contributing to DPN6, 7. Our previous study has shown that TLN markedly improves the neurological functions including thermal perception threshold and nerve conductivity in DPN rats by attenuating oxidative stress through the activation of Nrf[223]. The goal of the present study was to investigate whether TLN improves DPN by alleviating both oxidative and ER stress through modulating the PERK/Nrf[2] pathway
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