title: Molecular study of dietary heptadecane for the anti-inflammatory modulation of NF-kB in the aged kidney.
abstract: Heptadecane is a volatile component of Spirulina platensis, and blocks the de novo synthesis of fatty acids and ameliorates several oxidative stress-related diseases. In a redox state disrupted by oxidative stress, pro-inflammatory genes are upregulated by the activation of NF-kB via diverse kinases. Thus, the search and characterization of new substances that modulate NF-kB are lively research topics. In the present study, heptadecane was examined in terms of its ability to suppress inflammatory NF-kB activation via redox-related NIK/IKK and MAPKs pathway in aged rats. In the first part of the study, Fischer 344 rats, aged 9 and 20 months, were administered on average approximately 20 or 40 mg/Kg body weight over 10 days. The potency of heptadecane was investigated by examining its ability to suppress the gene expressions of COX-2 and iNOS (both NF-κB-related genes) and reactive species (RS) production in aged kidney tissue. In the second part of the study, YPEN-1 cells (an endothelial cell line) were used to explore the molecular mechanism underlying the anti-inflammatory effect of heptadecane by examining its modulation of NF-kB and NF-kB signal pathway. Results showed that heptadecane exhibited a potent anti-oxidative effect by protecting YPEN-1 cells from tert-butylhydroperoxide induced oxidative stress. Further molecular investigations revealed that heptadecane attenuated RS-induced NF-kB via the NIK/IKK and MAPKs pathways in YPEN-1 cells and aged kidney tissues. Based on these results, we conclude that heptadecane suppresses age-related increases in pro-inflammatory gene expressions by reducing NF-kB activity by upregulating the NIK/IKK and MAPKs pathways induced by RS. These findings provide molecular insight of the mechanisms by which heptadecane exerts its antiinflammatory effect in aged kidney tissues. We conclude that heptadecane suppresses age-related increases in pro-inflammatory gene expressions then travel upstream set by step by reducing NF-kB activity by downregulating the NIK/IKK and MAPKs pathways induced by RS.
authors.affiliation: Department of Pharmacy, College of Pharmacy, Aging Tissue Bank, Pusan National University, Busan, Republic of Korea.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Min Hi
authors.initials: MH
authors.lastname: Park
authors.forename: Yeon Ja
authors.initials: YJ
authors.lastname: Choi
authors.forename: Ki Wung
authors.initials: KW
authors.lastname: Chung
authors.forename: Chan Hum
authors.initials: CH
authors.lastname: Park
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Jang
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: An
authors.forename: Byung Pal
authors.initials: BP
authors.lastname: Yu
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000375:Aging; D000473:Alkanes / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D020122:tert-Butylhydroperoxide / Q000494:pharmacology; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D000473:Alkanes; D000893:Anti-Inflammatory Agents; D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; D016328:NF-kappa B; D052247:Nitric Oxide Synthase Type II; D017346:Protein Serine-Threonine Kinases; D020122:tert-Butylhydroperoxide; D000097782:NF-kappaB-Inducing Kinase; C496318:Nos2 protein, rat; C489691:Ptgs2 protein, rat; C016486:heptadecane
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