title: Nerve Regeneration Potential of Protocatechuic Acid in RSC96 Schwann Cells by Induction of Cellular Proliferation and Migration through IGF-IR-PI3K-Akt Signaling.
abstract: Peripheral nerve injuries, caused by accidental trauma, acute compression or surgery, often result in temporary or life-long neuronal dysfunctions and inflict great economic or social burdens on the patients. Nerve cell proliferation is an essential process to restore injured nerves of adults. Schwann cells play a crucial role in endogenous repair of peripheral nerves due to their ability to proliferate, migrate and provide trophic support to axons via expression of various neurotrophic factors, such as the nerve growth factor (NGF), especially after nerve injury. Protocatechuic acid (PCA) is a dihydroxybenzoic acid, a type of phenolic acid, isolated from the kernels of Alpinia oxyphylla Miq (AOF), a traditional Chinese herbal medicine the fruits of which are widely used as a tonic, aphrodisiac, anti-salivation and anti-diarrheatic. This study investigated the molecular mechanisms by which PCA induces Schwann cell proliferation by activating IGF-IR-PI3K-Akt pathway. Treatment with PCA induces phosphorylation of the insulin-like growth factor-I (IGF-I)-mediated phosphatidylinositol 3 kinase/serine - threonine kinase (PI3K/Akt) pathway, and activates expression of cell nuclear antigen (PCNA) in a dose-dependent manner. Cell cycle analysis after 18 h of treatment showed that proliferation of the RSC96 cells was enhanced by PCA treatment. The PCA induced proliferation was accompanied by modulation in the expressions of cell cycle proteins cyclin D1, cyclin E and cyclin A. Knockdown of PI3K using small interfering RNA (siRNA) and inhibition of IGF-IR receptor resulted in the reduction in cell survival proteins. The results collectively showed that PCA treatment promoted cell proliferation and cell survival via IGF-I signaling.
authors.affiliation: Department of Neurological Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 11490, Taiwan, Republic of China.
authors.forename: Da-Tong
authors.initials: DT
authors.lastname: Ju
authors.affiliation: Department of Healthcare Administration, Asia University, Taichung 41354, Taiwan, Republic of China.
authors.forename: Hung-En
authors.initials: HE
authors.lastname: Liao
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan, Republic of China.
authors.forename: Marthandam Asokan
authors.initials: MA
authors.lastname: Shibu
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, Republic of China.|Chinese Medicine Department, China Medical University Beigang Hospital, Yunlin 63244, Taiwan, Republic of China.
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.affiliation: Department of Biotechnology, Bharathyiar University, Coimbatore 641046, India.
authors.forename: Viswanadha Vijaya
authors.initials: VV
authors.lastname: Padma
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, Republic of China.
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.affiliation: Department of Hospital and Health Care Administration, Chia Nan University of Pharmacy & Science, Tainan County 71710, Taiwan, Republic of China.
authors.forename: Li-Chin
authors.initials: LC
authors.lastname: Chung
authors.affiliation: Department of Nursing, MeiHo University, Pingtung 91202, Taiwan, Republic of China.
authors.forename: Cecilia Hsuan
authors.initials: CH
authors.lastname: Day
authors.affiliation: Orthopaedic Department, Armed Forces General Hospital, Taichung 41152, Taiwan, Republic of China.
authors.forename: Chien-Chung
authors.initials: CC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan, Republic of China.|School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan, Republic of China.|Department of Health and Nutrition Biotechnology, Asia University, Taichung 41354, Taiwan, Republic of China.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D062385:Hydroxybenzoates / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D012583:Schwann Cells / Q000187:drug effects* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D062385:Hydroxybenzoates; C009091:protocatechuic acid; D019869:Phosphatidylinositol 3-Kinases; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt