The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Nitric Oxide-Induced Apoptosis of Human Dental Pulp Cells Is Mediated by the Mitochondria-Dependent Pathway

  • Park, Min Young (Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Jeong, Yeon Jin (Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Kang, Gi Chang (Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Kim, Mi-Hwa (Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Kim, Sun Hun (Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, Department of Oral Anatomy, School of Dentistry, Chonnam National University) ;
  • Chung, Hyun-Ju (Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, Department of Periodontology, School of Dentistry, Chonnam National University) ;
  • Jung, Ji Yeon (Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, Department of Oral Physiology, School of Dentistry, Chonnam National University) ;
  • Kim, Won Jae (Dental Science Research Institute and Medical Research Center for Biomineralization Disorders, Department of Oral Physiology, School of Dentistry, Chonnam National University)
  • Received : 2013.09.11
  • Accepted : 2014.01.08
  • Published : 2014.02.28
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Abstract

Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. NO is produced by nitric oxide synthase (NOS), and NOS is abundantly expressed in the human dental pulp cells (HDPCs). NO produced by NOS can be cytotoxic at higher concentrations to HDPCs. However, the mechanism by which this cytotoxic pathway is activated in cells exposed to NO is not known. The purpose of this study was to elucidate the NO-induced cytotoxic mechanism in HDPCs. Sodium nitroprusside (SNP), a NO donor, reduced the viability of HDPCs in a dose- and time-dependent manner. We investigated the in vitro effects of nitric oxide on apoptosis of cultured HDPCs. Cells showed typical apoptotic morphology after exposure to SNP. Besides, the number of Annexin V positive cells was increased among the SNP-treated HDPCs. SNP enhanced the production of reactive oxygen species (ROS), and N-acetylcysteine (NAC) ameliorated the decrement of cell viability induced by SNP. However, a soluble guanylate cyclase inhibitor (ODQ) did not inhibited the decrement of cell viability induced by SNP. SNP increased cytochrome c release from the mitochondria to the cytosol and the ratio of Bax/Bcl-2 expression levels. Moreover, SNP-treated HDPCs elevated activities of caspase-3 and caspase-9. While pretreatment with inhibitors of caspase (z-VAD-fmk, z-DEVD-fmk) reversed the NO-induced apoptosis of HDPCs. From these results, it can be suggested that NO induces apoptosis of HDPCs through the mitochondria-dependent pathway mediated by ROS and Bcl-2 family, but not by the cyclic GMP pathway.

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References

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