| Intracellular Signal Transduction Pathway of Leptin-Induced Apoptosis in
Human Bone Marrow Stromal Cells: ERK/cPLA2 and JAK-STAT1
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| 렙틴에 의한 사람 골수기질세포의 세포자멸을 일으키는
세포 내 신호전달 경로: ERK/cPLA2와 JAK-STAT1
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| 홍정수13,고정민,김승욱1,안정선3,김동관2,김기수 |
| 울산대학교 의과대학 서울아산병원 내과학교실, 아산생명과학연구소1, 흉부외과학교실2,
서울대학교 자연과학대학 생명과학부3
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| Abstract |
Background
Leptin, the Ob gene product, has recently emerged as a key regulator of bone mass. Previously, we observed that leptin induce apoptosis in human bone marrow stromal cells (hBMSC) via cytochrome c pathway with activating of caspase-9 and caspase-3, and cleavage of RARP. In this experiments, we further investigated the intracellular signal transduction pathway in leptin-induced apoptosis in hBMSC.
Methods
After the treatment of hBMSC with leptin, we examined MAPK (ERK, p38, JNK) and JAK/STAT1 signaling by Western blotting. The assay of arachidonic acid release from the cells into medium was used to determine the activity of cPLA2. Cell viability and activity of caspase-3 were determined using WST-1 assay and commercial kit, respectively. Release of cytochrome c from mitochondria into cytosol was measured by Western blotting.
Results
Leptin activated ERK, but not p38 and JNK, and up-regulated cPLA2 activity. The latter was abolished by pre-treatment of cells with the MEK inhibitor (PD98059 or U0126) or cPLA2 inhibitor (AACOCF3). PD98059, U0126 and AACOCF3 also diminished the leptin-induced cyrochrome c release into cytosol, decrease in cell viability and caspase-3 activation. In addition to the activation of ERK signaling, we demonstrated that leptin also stimulated JAK/STAT1 in hBMSC.
Conclusion
These data indicated that leptin induce apoptosis in hBMSC via ERK/cPLA2/cytochrome c pathway and via JAK/STAT1 pathway. To our knowledge, this is the first study demonstrating the intracellular signal transduction pathway of leptin on bone cells.
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| Key Words:
Leptin, Leptin receptor, Apoptosis, Human Bone Marrow Stromal Cells, Signal Tansduction Pathway |
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