title: Polyamines cause elevation of steroid 5α-reductase mRNA levels by suppressing mRNA degradation in C6 glioma cells.
abstract: Polyamines are widely distributed in living organisms, and considered to play a potential role in various cellular processes. The effects of polyamines on gene expression as well as cell proliferation have been suggested to be closely associated with the physiological and pathological functions. However, it seems necessary to investigate their potential roles in the regulation of cellular metabolism and functions. Previously, glial cells have been suggested to be involved in the protection and preservation of neuronal functions, probably through the production of neurotrophic factors in the brain. On the other hand, neuroactive 5α-reduced steroids promote glial cell differentiation, resulting in enhancement of their ability to produce brain-derived neurotrophic factor (BDNF). Based on these findings, polyamines are assumed to stimulate the expression of the gene encoding steroid 5α-reductase (5α-R), which can induce the production of neuroactive 5α-reduced steroids in glial cells. The effects of polyamines on 5α-R mRNA levels in C6 glioma cells were examined as a model experiment. In consequence, spermine (SPM) and spermidine (SPD), but not putrescine (PUT), have been shown to elevate 5α-R mRNA levels without activating the 5α-R promoter. Furthermore, SPM increased 5α-R mRNA levels under the conditions in which the mRNA biosynthesis was inhibited. Therefore, it can be speculated that polyamines increase 5α-R mRNA levels as a consequence of suppressing the degradation of mRNA.
authors.affiliation: Laboratory of Neuropharmacology, Department of Nursing, Shikoku University School of Health Sciences, Tokushima, 771-1192, Japan.
authors.forename: Kyoji
authors.initials: K
authors.lastname: Morita
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Lee
authors.forename: Song
authors.initials: S
authors.lastname: Her
authors.forename: Naoyoshi
authors.initials: N
authors.lastname: Nishibori
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D045744:Cell Line, Tumor; D005910:Glioma / Q000378:metabolism / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011073:Polyamines / Q000494:pharmacology*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D020871:RNA Stability / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D016329:Sp1 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D016376:Oligonucleotides, Antisense; D011073:Polyamines; D012333:RNA, Messenger; D016329:Sp1 Transcription Factor; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase
keywords: actinomycin D; mRNA stabilization; neuroactive steroids; promoter activity