Pim1 kinase provides protection against high glucose-induced stress and apoptosis in cultured dorsal root ganglion neurons. (August 2021)

• Record Type: Journal Article
• Authors: Liu, Yuantong; Shang, Yue; Yan, Zihan; Li, Hao; Wang, Zhen; Li, Zhenzhong; Liu, Zhen
• Is Part Of: Neuroscience research. Volume 169(2021)
• Page Start: 9
• Page End: 16
• Publication Date: 2021-08
• Subjects: DPN diabetic peripheral neuropathy -- PNS peripheral nervous system -- DRG dorsal root ganglion -- ER endoplasmic reticulum -- UPR unfolded protein response -- Pim proviral integration site for moloney murine leukemia virus -- STZ streptozotocin -- HG high glucose -- NG normal glucose; Diabetic peripheral neuropathy -- Oxidative stress -- Endoplasmic reticulum stress -- Apoptosis -- Dorsal root ganglion -- Pim1 kinase; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2020.06.004
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: Hyperglycemia induces compensatory upregulation of Pim1 kinase in the DRG neurons. Pharmacological inhibition of Pim1 accelerates the apoptosis of the DRG neurons in vitro. Pharmacological inhibition of Pim1 in vitro sensitizes DRG neurons to oxidative stress and ER stress induced by high glucose. Abstract: The pathogenesis of diabetic peripheral neuropathy (DPN) is complex and not well understood. Recently, oxidative stress and endoplasmic reticulum (ER) stress induced by hyperglycemia have been demonstrated to play a critical role in neuronal apoptosis, which then contributing to DPN. However, the specific molecular mechanism that underlies the hyperglycemia-induced neuronal stresses and apoptosis remains largely unknown. In this study, we demonstrated for the first time that Pim1 kinase is a positive modulator of dorsal root ganglion (DRG) neuron survival in vitro. Hyperglycemia causes compensatory upregulation of Pim1 kinase in the DRG neurons, which provides protection against high glucose-induced oxidative stress and ER stress. Pharmacological inhibition of Pim1 not only sensitizes the stress response to high glucose in the DRG neurons, but also accelerates the apoptosis of DRG neurons in vitro. Therefore, our work provides experimental evidence for the prevention of high glucose-induced neuronal stress and apoptosis by targeting Pim1 kinase.