Human telomerase reverse transcriptase의 extra-telomeric function을 모방하는 novel vaccine peptide GV1001에 의한 β-amyloid 독성의 효과적인 차단

Abstract

GV1001은 human telomerase reverse transcriptase에서 유래된 펩타이드 서열 611-626을 사용한 백신이다. 본 논문에서는 rat neural stem cells (NSCs)에서 oligomeric β-amyloid (Aβ)로 유도된 neurotoxicity에 대한 GV1001의 효과를 조사하였다. Primary culture NSCs에 여러 농도의 GV1001과 Aβ25-35 oligome를 48시간 동안 처리 후 관찰 하였다. Aβ25-35 oligomer로 유도된 neurotoxicity에 대한 GV1001의 보호효과는 농도 의존적으로 작용하였다. Aβ25-35 oligomer의 농도 의존적으로 감소하였던 NSCs의 viability, proliferation, 와 mobilization이 GV1001 처리에 의하여 대조군 수준으로 회복하였고 Aβ25-35 oligomer에 의해 증가되었던 NSCs의 free radical levels GV1001 처리에 의하여 감소함을 확인했다. 또한 GV1001의 처리로 Aβ25-35 oligomer로 인하여 손상된 NSCs intracellular의 survival 관련 protein과 mitochondria의 survival 관련 protein의 발현 증가를 확인하고, death 관련 protein과 inflammation 관련 protein, mitochondria의 death 관련 protein의 발현 감소를 확인하였다. human telomerase reverse transcriptase의 extra-telomeric은 cellular proliferation, anti-apoptotic 효과, mitochondrial stabilization, anti-aging 그리고 anti-oxidant 효과 등의 기능을 하고 있는데 Aβ25-35 oligomer로 유도된 neurotoxicity에 대한 GV1001의 작용들을 확인한 결과 Aβ25-35 oligomer에 대한 GV1001의 보호효과는 human telomerase reverse transcriptase의 extra-telomeric 기능을 모방함에 의한 것으로 판단되어 진다. |GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase (hTERT) sequence. We investigated the effects of GV1001 against amyloid beta (Aβ) oligomer-induced neurotoxicity in rat neural stem cells (NSCs). Primary culture NSCs were treated with several concentrations of GV1001 and/or Aβ25-35 oligomer for 48 hr. GV1001 protected NSCs against the Aβ25-35 oligomer in a concentration-dependent manner. Aβ25-35 concentration dependently decreased viability, proliferation and mobilization of NSCs and GV1001 treatment restored the cells to wild-type levels. Aβ25-35 increased free radical levels in rat NSCs while combined treatment with GV1001 significantly reduced these levels. In addition, GV1001 treatment of Aβ25-35-injured NSCs increased the expression level of survival-related proteins, including mitochondria-associated survival proteins, and decreased the levels of death and inflammation-related proteins, including mitochondria-associated death proteins. Together, these results suggest that GV1001 possesses neuroprotective effects against Aβ25-35 oligomer in NSCs and that these effects are mediated through mimicking the extra-telomeric functions of hTERT, including the induction of cellular proliferation, anti-apoptotic effects, mitochondrial stabilization, anti-aging and anti-oxidant effects.; GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase (hTERT) sequence. We investigated the effects of GV1001 against amyloid beta (Aβ) oligomer-induced neurotoxicity in rat neural stem cells (NSCs). Primary culture NSCs were treated with several concentrations of GV1001 and/or Aβ25-35 oligomer for 48 hr. GV1001 protected NSCs against the Aβ25-35 oligomer in a concentration-dependent manner. Aβ25-35 concentration dependently decreased viability, proliferation and mobilization of NSCs and GV1001 treatment restored the cells to wild-type levels. Aβ25-35 increased free radical levels in rat NSCs while combined treatment with GV1001 significantly reduced these levels. In addition, GV1001 treatment of Aβ25-35-injured NSCs increased the expression level of survival-related proteins, including mitochondria-associated survival proteins, and decreased the levels of death and inflammation-related proteins, including mitochondria-associated death proteins. Together, these results suggest that GV1001 possesses neuroprotective effects against Aβ25-35 oligomer in NSCs and that these effects are mediated through mimicking the extra-telomeric functions of hTERT, including the induction of cellular proliferation, anti-apoptotic effects, mitochondrial stabilization, anti-aging and anti-oxidant effects.