Inhibition of neutral sphingomyelinase decreases elevated levels of inducible nitric oxide synthase and apoptotic cell death in ocular hypertensive rats

Aslan M., Basaranlar G., ÜNAL M., Ciftcioglu A., DERİN N., Mutus B.

TOXICOLOGY AND APPLIED PHARMACOLOGY, cilt.280, sa.3, ss.389-398, 2014 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 280 Sayı: 3
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1016/j.taap.2014.08.026
  • Dergi Adı: TOXICOLOGY AND APPLIED PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.389-398
  • Anahtar Kelimeler: Ocular hypertension, Endoplasmic reticulum stress, Neutral sphingomyelinase, Inducible nitric oxide synthase, Protein nitration, Caspase, ENDOPLASMIC-RETICULUM STRESS, OXIDATIVE STRESS, PROTEIN INTERACTIONS, MEDIATED APOPTOSIS, EXPRESSION, CERAMIDE, ROLES, CHOLESTEROL, ASTROCYTES, INDUCTION
  • Akdeniz Üniversitesi Adresli: Evet

Özet

Endoplasmic reticulum (ER) stress and excessive nitric oxide production via induction of inducible nitric oxide synthase (NOS2) have been implicated in the pathogenesis of neuronal retinal cell death in ocular hypertension. Neutral sphingomyelinase (N-SMase)/ceramide pathway can regulate NOS2 expression, hence this study determined the role of selective neutral sphingomyelinase (N-SMase) inhibition on retinal NOS2 levels, ER stress, apoptosis and visual evoked potentials (VEPs) in a rat model of elevated intraocular pressure (EIOP). NOS2 expression and retinal protein nitration were significantly greater in EIOP and significantly decreased with N-SMase inhibition. A significant increase was observed in retinal ER stress markers pPERK, CHOP and GRP78 in EIOP, which were not significantly altered by N-SMase inhibition. Retinal TUNEL staining showed increased apoptosis in all EIOP groups; however N-SMase inhibition significantly decreased the percent of apoptotic cells in EIOP. Caspase-3, -8 and -9 activities were significantly increased in EIOP and returned to baseline levels following N-SMase inhibition. Latencies of all VEP components were significantly prolonged in EIOP and shortened following N-SMase inhibition. Data confirm the role of nitrative injury in EIOP and highlight the protective effect of N-SMase inhibition in EIOP via down-regulation of NOS2 levels and nitrative stress. (C) 2014 Elsevier Inc. All rights reserved.