title: Protective function of pyridoxamine on retinal photoreceptor cells via activation of the p‑Erk1/2/Nrf2/Trx/ASK1 signalling pathway in diabetic mice.
abstract: The present study aimed to investigate the mechanisms that mediate the protective effects of pyridoxamine (PM) on light‑damaged retinal photoreceptor cells in diabetic mice. A high‑fat diet and streptozotocin were used to induce a mouse model of type II diabetes. During the experiment, mice were divided the mice into three types of group, as follows: Control groups (negative control and light‑damaged groups); experimental groups (diabetic and diabetic light‑damaged groups); and treatment groups (25, 50 and 100 mg/kg PM‑treated groups). Using hematoxylin‑eosin staining, the number of nuclear layer cells were counted. Western blotting and immunohistochemistry were performed to measure the levels of thioredoxin (Trx), phospho‑extracellular signal‑regulated kinase 1/2 (p‑Erk1/2), nuclear factor erythroid 2‑related factor 2 (Nrf2) and apoptosis signal‑regulating kinase 1 (ASK1). The photoreceptor cell count in the outer nuclear layer of the light‑damaged, diabetic control and diabetic light‑damaged groups were significantly reduced compared with the negative control group (P<0.001). The cell counts in the PM‑treated groups were significantly increased compared with the diabetic group (P<0.001). Compared with the negative control group, the light‑damaged, diabetic and diabetic light‑damaged groups exhibited significantly decreased Trx, p‑Erk1/2 and Nrf2 expression levels (P<0.001), and significantly increased ASK1 expression levels (P<0.001). However, in the PM‑treated groups, Trx, p‑Erk1/2 and Nrf2 expression levels were significantly increased (P<0.001), and ASK1 expression was significantly decreased (P<0.001). The results of the present study demonstrate that PM protects retinal photoreceptor cells against light damage in diabetic mice, and that its mechanism may be associated with the upregulation of Trx, p‑Erk1/2 and Nrf2 expression, and the downregulation of ASK1 expression.
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Chenghong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Jinlei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Histology and Embryology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Kong
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007333:Insulin Resistance; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects; D020011:Protective Agents / Q000494:pharmacology*; D011733:Pyridoxamine / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D020011:Protective Agents; C515559:Txn1 protein, mouse; D013879:Thioredoxins; D011733:Pyridoxamine; D048848:MAP Kinase Kinase Kinase 5