Publication: Role of cathepsin B in dengue virus-mediated apoptosis
Issued Date
2013-08-16
Resource Type
ISSN
10902104
0006291X
0006291X
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2-s2.0-84881558159
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Mahidol University
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SCOPUS
Bibliographic Citation
Biochemical and Biophysical Research Communications. Vol.438, No.1 (2013), 20-25
Suggested Citation
Atthapan Morchang, Jutatip Panaampon, Aroonroong Suttitheptumrong, Umpa Yasamut, Sansanee Noisakran, Pa thai Yenchitsomanus, Thawornchai Limjindaporn Role of cathepsin B in dengue virus-mediated apoptosis. Biochemical and Biophysical Research Communications. Vol.438, No.1 (2013), 20-25. doi:10.1016/j.bbrc.2013.07.009 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/31243
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Title
Role of cathepsin B in dengue virus-mediated apoptosis
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Abstract
Dengue virus (DENV) infection is one of the most important mosquito-borne viral diseases, which is endemic in the tropical and sub-tropical regions. Patients with dengue hemorrhagic fever (DHF) generally present hemorrhagic tendencies, plasma leakage, thrombocytopenia, and hemoconcentration. Hepatic dysfunction is also a crucial feature of DENV infection. Hepatic biopsy specimens obtained from fatal cases of DENV infection show cellular apoptosis, which apparently relate to the pathogenesis. Cathepsins, which are cysteine proteases inside the lysosome, were previously reported to be up-regulated in patients with DHF. However, their functions during DENV infection have not been thoroughly investigated. We show for the first time that DENV induces lysosomal membrane permeabilization. The resulting cytosolic cathepsin B and S contributed to apoptosis via caspase activation. The activity of caspase 3 was significantly reduced in DENV-infected HepG2 cells treatedwith cathepsin B or S inhibitors. Treatment with cathepsin B inhibitor also reduced the activity of caspase 9, suggesting that cathepsin B activates both caspase-9 and caspase-3. Reduced cathepsin B expression, effected by RNA interference, mimicked pharmacological inhibition of the enzyme and confirmed the contribution of cathepsin B to apoptotic events induced by DENV in HepG2 cells. © 2013 Elsevier Inc.