title: Calcitriol prevents peripheral RSC96 Schwann neural cells from high glucose & methylglyoxal-induced injury through restoration of CBS/H2S expression.
abstract: A meta-analysis has suggested that vitamin D deficiency is involved in diabetic peripheral neuropathy (DPN) and the levels of hydrogen sulfide (H2S) are also decreased in type 2 diabetes. The injection of vitamin D induces cystathionine-β-synthase (CBS) expression and H2S generation. However, it remains unclear whether the supplementation of vitamin D prevents DPN through improvement of CBS/H2S expression. In the present study, RSC96 cells, a rat Schwann cell line, were exposed to high glucose and methylglyoxal (HG&MG) to simulate diabetic peripheral nerve injury in vivo. Before the exposure to HG&MG, the cells were preconditioned with calcitriol (CCT), an active form of vitamin D, and then CCT-mediated neuroprotection was investigated in respect of cellular viability, superoxide anion (O2(-)) generation, inducible nitric oxide (NO) synthase (iNOS)/NO expression, mitochondrial membrane potential (MMP), as well as CBS expression and activity. It was found that both high glucose and MGO decreased cell viability and co-treatment with the two induced a more serious injury in RSC96 cells. Therefore, the exposure to HG&MG was used in the present study. The exposure to HG&MG markedly induced iNOS expression, NO and O2(-) generation, as well as MMP loss. In addition, the exposure to HG&MG depressed CBS expression and activity in RSC96 cells. However, the preconditioning with CCT significantly antagonized HG&MG-induced cell injury including the decreased viability, iNOS overexpression, NO and O2(-) accumulation, as well as MMP loss. CCT also partially restored the decreased CBS expression and activity triggered by HG&MG, while the inhibition of CBS with hydroxylamine attenuated CCT-mediated neuroprotection. Moreover, the exogenous donation of H2S produced similar cellular protective effects to CCT. The data indicate that the supplementation of vitamin D prevents HG&MG-induced peripheral nerve injury involving the restoration of endogenous H2S system, which may provide a basal support for the treatment of DPN with vitamin D clinically.
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou 511436, China; Quality Control Section of Academic Affairs, Guangzhou Medical University, Guangzhou 511436, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: Zhuang
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou 511436, China.
authors.forename: Fu-hui
authors.initials: FH
authors.lastname: Meng
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou 511436, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Xiao-bian
authors.initials: XB
authors.lastname: Dong
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou 511436, China.
authors.forename: Guo-Hui
authors.initials: GH
authors.lastname: Liu
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou 511436, China; Quality Control Section of Academic Affairs, Guangzhou Medical University, Guangzhou 511436, China.
authors.forename: Jian-hua
authors.initials: JH
authors.lastname: Li
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou 511436, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Dong
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou 511436, China.
authors.forename: Ji-de
authors.initials: JD
authors.lastname: Xu
authors.affiliation: Department of Physiology, Guangzhou Medical University, Guangzhou 511436, China. Electronic address: yang-chuntao@163.com.
authors.forename: Chun-tao
authors.initials: CT
authors.lastname: Yang
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003541:Cystathionine beta-Synthase / Q000096:biosynthesis*; D005947:Glucose / Q000633:toxicity*; D006862:Hydrogen Sulfide / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D030421:Peroxynitrous Acid / Q000378:metabolism; D011765:Pyruvaldehyde / Q000633:toxicity*; D051381:Rats; D012583:Schwann Cells / Q000187:drug effects*; D013481:Superoxides / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D013481:Superoxides; D030421:Peroxynitrous Acid; D011765:Pyruvaldehyde; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D003541:Cystathionine beta-Synthase; D002117:Calcitriol; D005947:Glucose; D006862:Hydrogen Sulfide
keywords: Diabetic peripheral neuropathy; Hydrogen sulfide; Inducible nitric oxide synthase; Methylglyoxal; Mitochondrial function; Vitamin D