title: Attenuated neuroprotective effect of riboflavin under UV-B irradiation via miR-203/c-Jun signaling pathway in vivo and in vitro.
abstract: BACKGROUND
  Riboflavin (RF) or vitamin B2 is known to have neuroprotective effects. In the present study, we report the attenuation of the neuroprotective effects of RF under UV-B irradiation. Preconditioning of UV-B irradiated riboflavin (UV-B-RF) showed attenuated neuroprotective effects compared to that of RF in SH-SY5Y neuroblostoma cell line and primary cortical neurons in vitro and a rat model of cerebral ischemia in vivo.
  
  
  RESULTS
  Results indicated that RF pretreatment significantly inhibited cell death and reduced LDH secretion compared to that of the UV-B-RF pretreatment in primary cortical neuron cultures subjected to oxygen glucose deprivation in vitro and cortical brain tissue subjected to ischemic injury in vivo. Further mechanistic studies using cortical neuron cultures revealed that RF treatment induced increased miR-203 expression which in turn inhibited c-Jun expression and increased neuronal cell survival. Functional assays clearly demonstrated that the UV-B-RF preconditioning failed to sustain the increased expression of miR-203 and the decreased levels of c-Jun, mediating the neuroprotective effects of RF. UV-B irradiation attenuated the neuroprotective effects of RF through modulation of the miR-203/c-Jun signaling pathway.
  
  
  CONCLUSIONS
  Thus, the ability of UV-B to serve as a modulator of this neuroprotective signaling pathway warrants further studies into its role as a regulator of other cytoprotective/neuroprotective signaling pathways.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Tripathi
authors.forename: Ashish
authors.initials: A
authors.lastname: Dwivedi
authors.forename: Manish Kumar
authors.initials: MK
authors.lastname: Pal
authors.forename: Namrata
authors.initials: N
authors.lastname: Rastogi
authors.forename: Priyanka
authors.initials: P
authors.lastname: Gupta
authors.forename: Shakir
authors.initials: S
authors.lastname: Ali
authors.forename: Manjunatha B H
authors.initials: MB
authors.lastname: Prabhu
authors.forename: Hari Narayan
authors.initials: HN
authors.lastname: Kushwaha
authors.forename: Ratan Singh
authors.initials: RS
authors.lastname: Ray
authors.forename: Shio Kumar
authors.initials: SK
authors.lastname: Singh
authors.forename: Shivali
authors.initials: S
authors.lastname: Duggal
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Narayan
authors.affiliation: Division of Endocrinology, CSIR-Central Drug Research Institute, Jankipuram Extension, Lucknow 226031, India. dpm@cdri.res.in.
authors.forename: Durga Prasad
authors.initials: DP
authors.lastname: Mishra
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000096:biosynthesis* / Q000235:genetics; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D018696:Neuroprotective Agents / Q000008:administration & dosage; D051381:Rats; D012256:Riboflavin / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: C546703:MIRN203 microRNA, human; D035683:MicroRNAs; D018696:Neuroprotective Agents; D048031:JNK Mitogen-Activated Protein Kinases; D012256:Riboflavin