Protective effect of cyclo(His-Pro) on streptozotocin-induced cytotoxicity and apoptosis in vitro

Kwang Bon, Hyung Joo Suh, Kyung Soo Ra, Jang Won Choi

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Cyclo(His-Pro) (CHP) is a naturally occurring, cyclic dipeptide structurally related to thyrotropin-releasing hormone (TRH). CHP was efficiently obtained from soybean meal by hydrolysis with flavourzyme and alcalase. In this study, the effects of CHP on streptozotocin (STZ)-induced β-cell dysfunction and apoptosis were investigated in rat insulinoma cells (RINm5F) secreting insulin. When the RINm5F cells were treated with 2mM STZ, insulin secretion decreased to approximately 54% that of control cells. However, CHP treatment restored the insulin-secreting activity of RINm5F cells to approximately 71% that of the untreated control cells. Moreover, CHP significantly protected the cells from STZ-mediated cytotoxicity via reduction of nitric oxide (NO) production (2.3-fold) and lipid peroxidation (1.9-fold), which were induced by STZ. Moreover, CHP treatment also attenuated STZ-induced apoptotic events, such as activation of caspase-3, poly(ADP-ribose) polymerase (PARP) cleavage, and DNA fragmentation in RINm5F cells, indicating that CHP could protect the cells from apoptotic cell death induced by oxidative stress of STZ by increasing the expression of an anti-apoptotic protein, Bcl-2. These results suggest that CHP could be a candidate material for a protective and therapeutic agent against STZ-mediated cytotoxicity and apoptosis

Original languageEnglish
Pages (from-to)218-227
Number of pages10
JournalJournal of Microbiology and Biotechnology
Volume21
Issue number2
DOIs
Publication statusPublished - 2011 Feb 1

Fingerprint

Streptozocin
Apoptosis
Insulin
Subtilisins
Protective Agents
Insulinoma
Apoptosis Regulatory Proteins
Thyrotropin-Releasing Hormone
Poly(ADP-ribose) Polymerases
histidyl-proline diketopiperazine
In Vitro Techniques
Dipeptides
Insulin-Secreting Cells
DNA Fragmentation
Soybeans
Caspase 3
Lipid Peroxidation
Meals
Nitric Oxide
Oxidative Stress

Keywords

  • Apoptotic events
  • Cyclo(His-Pro)
  • Nitric oxide
  • RINm5F
  • Streptozotocin

ASJC Scopus subject areas

  • Biotechnology
  • Applied Microbiology and Biotechnology

Cite this

Protective effect of cyclo(His-Pro) on streptozotocin-induced cytotoxicity and apoptosis in vitro. / Bon, Kwang; Suh, Hyung Joo; Ra, Kyung Soo; Choi, Jang Won.

In: Journal of Microbiology and Biotechnology, Vol. 21, No. 2, 01.02.2011, p. 218-227.

Research output: Contribution to journalArticle

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abstract = "Cyclo(His-Pro) (CHP) is a naturally occurring, cyclic dipeptide structurally related to thyrotropin-releasing hormone (TRH). CHP was efficiently obtained from soybean meal by hydrolysis with flavourzyme and alcalase. In this study, the effects of CHP on streptozotocin (STZ)-induced β-cell dysfunction and apoptosis were investigated in rat insulinoma cells (RINm5F) secreting insulin. When the RINm5F cells were treated with 2mM STZ, insulin secretion decreased to approximately 54{\%} that of control cells. However, CHP treatment restored the insulin-secreting activity of RINm5F cells to approximately 71{\%} that of the untreated control cells. Moreover, CHP significantly protected the cells from STZ-mediated cytotoxicity via reduction of nitric oxide (NO) production (2.3-fold) and lipid peroxidation (1.9-fold), which were induced by STZ. Moreover, CHP treatment also attenuated STZ-induced apoptotic events, such as activation of caspase-3, poly(ADP-ribose) polymerase (PARP) cleavage, and DNA fragmentation in RINm5F cells, indicating that CHP could protect the cells from apoptotic cell death induced by oxidative stress of STZ by increasing the expression of an anti-apoptotic protein, Bcl-2. These results suggest that CHP could be a candidate material for a protective and therapeutic agent against STZ-mediated cytotoxicity and apoptosis",
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