title: Histone Deacetylase 2 in Sudden Sensorineural Hearing Loss Patients in Response to Intratympanic Methylprednisolone Perfusion.
abstract: OBJECTIVE
  To evaluate the expression of histone deacetylase 2 (HDAC2) in peripheral blood mononuclear cells (PBMCs) from patients with sudden sensorineural hearing loss (SSNHL) who were refractory to systemic glucocorticoid treatment and to identify the relationship between the level of HDAC2 and glucocorticoid insensitivity.
  
  
  METHODS
  Prospective clinical study.
  
  
  METHODS
  This study was conducted in Nanjing Drum Tower Hospital, Nanjing University Medical School.
  
  
  METHODS
  PBMCs were collected from 42 refractory SSNHL patients. After a 10-day intratympanic methylprednisolone perfusion (IMP) and systemic Ginkgo biloba extract treatment, the SSNHL patients were divided into 2 groups according to their hearing recovery after IMP (IMP sensitive and insensitive). Real-time polymerase chain reaction and HDAC2 protein assays were used to detect the relative expression levels of HDAC2 in PBMCs. The HDAC2 mRNA expression and protein levels in PBMCs collected from 17 volunteers were used as normal HDAC2 reference levels.
  
  
  RESULTS
  Compared with normal reference levels, HDAC2 protein levels were significantly reduced, while the HDAC2 mRNA expression was much higher in all refractory SSNHL patients before IMP. HDAC2 mRNA expression and HDAC2 protein levels were significantly elevated in the IMP-sensitive group, while no change was observed in the IMP-insensitive group after IMP plus systemic antioxidant treatment.
  
  
  CONCLUSIONS
  Reduced HDAC2 protein levels may be 1 of the mechanistic underpinnings of corticosteroid insensitivity in refractory SSNHL patients. IMP can increase HDAC2 protein levels and the expression of HDAC2 mRNA in IMP-sensitive patients. HDAC2 protein levels might be regulated through posttranslational modifications.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Hou
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China shewandong@163.com.
authors.forename: Wandong
authors.initials: W
authors.lastname: She
authors.affiliation: Hough Ear Institute, Oklahoma City, Oklahoma, USA.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Dai
authors.affiliation: Department of Otolaryngology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Xie
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nanjing Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
authors.forename: Qiongqiong
authors.initials: Q
authors.lastname: Zhou
mesh_terms: D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D006319:Hearing Loss, Sensorineural / Q000188:drug therapy* / Q000201:enzymology*; D056464:Histone Deacetylase 2 / Q000096:biosynthesis*; D006801:Humans; D000069555:Injection, Intratympanic; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D010477:Perfusion; D011446:Prospective Studies; D017211:Treatment Failure
chemical_list: D005938:Glucocorticoids; D056464:Histone Deacetylase 2; D008775:Methylprednisolone
keywords: glucocorticoid resistance; histone deacetylase 2; posttranslational modification; sudden sensorineural hearing loss