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Metformin에 의해 발생한 H4IIE 간암세포의 세포사멸 과정에서 자가포식의 역할
백근호,박덕배,Baek, Keunho,Park, Deokbae 제주대학교 의과학연구소 2020 The Journal of Medicine and Life Science Vol.17 No.2
Metformin, a predominantly prescribed anti-diabetic drug for decades, has gained new insights for its anti-tumor activity in a variety of cancer cells. Our previous studies also showed the obvious pro-apoptotic activity of metformin and the underlying action mechanisms in hepatocellular carcinoma cells. Together with apoptosis, autophagy is a crucial intracellular process to determine the survival or death of cells under some stressful environments. The present study aimed to determine the role of autophagy in metformin-induced death of H4IIE hepatocellular carcinoma cells. Metformin blocked the formation of autophagosome and the expression of LC3A, generally described as a biomarker of autophagy. Inhibition of AMPK reversed the metformin-induced blockade of autophagy. Antioxidant (NAC) suppressed the metformin-induced cell death but not affected LC3A. The inhibition of protein kinase C totally restored the metformin-suppressed expression of LC3A. In summary, our present study suggests that autophagy is an anti-apoptotic player in metformin-induced apoptosis in H4IIE cells.
이영기(Youngki Lee),박덕배(Deokbae Park),장가용(Ka Young Chang) 대한해부학회 2001 Anatomy & Cell Biology Vol.34 No.1
고장액성식염수의 투여는 흰쥐의 시상하부에 위치하고 있는 거대신경세포에서 c-Fos를 발현하는 것으로 알려졌다. 본 연구는 면역조직화학적 이중염색을 이용하여 고장액의 자극에 반응하여 c-Fos를 발현하는 신경세포를 동정하고자 계획되 었다. 고장액성식염수는 시상하부의 SON, PVN 지역 이외에도 여러 부분에서 c-Fos에 대한 면역양성반응을 보여 주었다. 또한 c-Fos에 대한 면역양성을 나타내는 oxytocin신경세포는 PVN, SON에서 뿐만 아니라 preoptic area나 accessory nuclei에서도 관찰되었다. 특히 accessory nuclei에서는 거의 모든 oxytocin 신경세포에서 c-Fos가 발현되었다. oxytocin이나 vasopressin에 대한 면역양성을 보여주지 않는 c-Fos 면역양성세포도 다수 관찰되었으며, 고장액에 의한 c-Fos의 발현은 vasopressin 신경세포보다는 oxytocin 신경세포에서 보다 많은 발현빈도를 보여 주었다. 이러한 연구결과는 oxytocin 신경세포와 vasopressin 신경세포 모두가 삼투농도에 반응하며 또한 c-Fos를 발현함으로써 활성화됨을 보여준다. Previous studies have shown that hypertonic saline induces c-fos expression in the magnocellular neurons of rat hypothalamus. The present immunohistochemical double-labeling study was undertaken to determine the identification of magnocellular neurons expressing c-Fos in response to osmotic stimulus. Hypertonic saline induced c-Fos-like immunoreactivity (FLI) in various regions of hypothalamus in addition to supraoptic nucleus (SON) and paraventricular nucleus (PVN). FLI was detected in most of oxytocin neurons in the preoptic region and in the accessory nuclei located between the PVN and SON as well as in the SON and PVN. In particular, most of all oxytocin neurons in the accessory nuclei were labeled for c-Fos. There were also many FLI cells that did not show oxytocin and vasopressin immunoreacitivity in their cytoplasm. Relative frequencies of oxytocin and vasopressin neuronal responses showed that much more cells of oxytocin than vasopressin were induced to express c-fos in response to hypertonic saline. These data show that both oxytocin and vasopressin neurons are sensitive to osmotic stimulus and activated via expression of c-Fos by hypertonic saline.