Reduction in ins-7 gene expression in non-neuronal cells of high glucose exposed Caenorhabditis elegans protects from reactive metabolites, preserves neuronal structure and head motility, and prolongs lifespan
| Autor: | Christin Riedinger, Nadine Volk, Michael Mendler, Stephan Herzig, Thomas Fleming, Michael Morcos, Andrea Schlotterer, Peter P. Nawroth |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Glycation End Products Advanced Endocrinology Diabetes and Metabolism medicine.medical_treatment Peptide Hormones Longevity Motility Diabetic Neuropathy Glycation/age Insulin Action Neuronal Function Oxidative Stress/ros Biology medicine.disease_cause Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound Gene Knockout Techniques Endocrinology Glycation Internal Medicine medicine Animals Caenorhabditis elegans Caenorhabditis elegans Proteins chemistry.chemical_classification Feedback Physiological Reactive oxygen species Behavior Animal Superoxide Dismutase Insulin Methylglyoxal Osmolar Concentration Lactoylglutathione Lyase Gene Expression Regulation Developmental Survival Analysis Neuroprotection Oxidative Stress 030104 developmental biology Glucose Biochemistry chemistry Gene Knockdown Techniques Mutation biology.protein Advanced glycation end-product RNA Interference Reactive Oxygen Species Oxidative stress |
| Zdroj: | J. Diab. Complic. 31, 304-310 (2017) |
| Popis: | Background Glucose derived metabolism generates reactive metabolites affecting the neuronal system and lifespan in C. elegans . Here, the role of the insulin homologue ins-7 and its downstream effectors in the generation of high glucose induced neuronal damage and shortening of lifespan was studied. Results In C. elegans high glucose conditions induced the expression of the insulin homologue ins-7 . Abrogating ins-7 under high glucose conditions in non-neuronal cells decreased reactive oxygen species (ROS)-formation and accumulation of methylglyoxal derived advanced glycation endproducts (AGEs), prevented structural neuronal damage and normalised head motility and lifespan. The restoration of lifespan by decreased ins-7 expression was dependent on the concerted action of sod-3 and glod-4 coding for the homologues of iron-manganese superoxide dismutase and glyoxalase 1, respectively. Conclusions Under high glucose conditions mitochondria-mediated oxidative stress and glycation are downstream targets of ins-7. This impairs the neuronal system and longevity via a non-neuronal/neuronal crosstalk by affecting sod-3 and glod-4 , thus giving further insight into the pathophysiology of diabetic complications. |
| Databáze: | OpenAIRE |
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