Changes in Mitogen-activated Protein Kinase Activities During Acidification-induced Apoptosis in CHO Cells
1
조회
0
다운로드
1
인용
0
참고문헌
초록
Abstract
Homeostatic pH is very important for various cellular processes, including metabolism, survival, and death. An imbalanced-pH might induce cellular acidosis, which is involved in many abnormal events such as apoptosis and malignancy. One of several factors contributing to the onset of metabolic acidosis is the production of lactate and protons by lactate dehydrogenase (LDH) in anaerobic glycolysis. LDH is an important enzyme that catalyzes the reversible conversion of pyruvate to lactate. This study sought to examine whether decreases in extracellular pH induce apoptosis of CHO cells, and to elucidate the role of mitogen-activated protein kinases (MAPKs) in acidificationinduced apoptosis. To test apoptotic signaling by acidification we used CHO dhfr- cells that were sensitive to acidification, and CHO/anti-LDH cells that are resistant to acidification-induced apoptosis and have reduced LDH activity by stable LDH antisense mRNA expression. In the present study, cellular lactic acid-induced acidification and the role of MAPKs signaling in acidification-induced apoptosis were investigated. Acidification, which is caused by HCO3 --free conditions, induced apoptosis and MAPKs (ERK, JNK, and p38) activation. However, MAPKs were slightly activated in acidic conditions in the CHO/anti-LDH cells, indicating that lactic acid-induced acidification induces activation of MAPKs. Treatment with a p38 inhibitor, PD169316, increased acidification-induced apoptosis but apoptosis was not affected by inhibitors for ERK (U0126) or JNK (SP600125) Thus, these data support the hypothesis that activation of the p38 MAPK during acidificationinduced apoptosis contributes to cell survival.
참고문헌 (28)
- "Apoptosis inhibitory activity of cytoplasmic p21(Cip1", WAF1) in monocytic diferentiation., 1999, pp.18, 1223~1234
- "Regulation of intracellular pH", 28, pp.160~179 (2004)
- "The importance of intracellular pH in the regulation of cel function", 20, pp.139~150 (2003)
- "Mammalian MAP kinase signaling cascades", 410, pp.37~40 (2001)
- "The mitogen-activated protein kinase signal transduction pathway.", 268, pp.14553~14556 (1993)
- "p38 MAPK mediates acid-induced transcription of PEPCK in LLC-PK", 283, pp.678~688 (2002)
- "Intracellular acidification induces apoptosis by stimulating ICE-like protease activity", 110, pp.653~661 (1997)
- "The proton-linked mono-carboxylate transporter (MCT) family: structure, function and regulation", 343, pp.281~299 (1999)
- "Intracellular acidification trigered by mitochondrial-derived hydrogen 90 Jin Young Ki et al. peroxide is an effector mechanism for drug-induced apoptosis in tumor cells.", 276, pp.514~521 (2001)
- "Blocking of acidosis-mediated apoptosis by a reduction of lactate dehydrogenase activity through antisense mRNA expression", 289, pp.141~1149 (2001)
- "Lactate transport in skeletal muscle-role and regulation of the monocarboxylate transporter", 517, pp.633~642 (1999)
- "diferential expression by neoplastic and stromal cels in non-smal cell lung cancer and other epithelial malignant tumors", 24, pp.199~202 (2003)
- "Single-cell analysis of the intracellular pH and its regulation during the monocytic diferentiation of U937 human leukemic cels", pp.455~460
- "Caspase-8-mediated intracellular acidification precedes mitochondrial dysfunction in somatostatin-induced apoptosis", 275, pp.9244~9250 (2000)
- "Apoptosis of murine thymocytes induced by extracellular ATP is dose-and cytosolic pH-dependent", 72, pp.23~30 (2000)
- "Change in lactate production in Myc-transformed cells precedes apoptosis and can be inhibited by Bcl-2 overexpression", 446, pp.38~342 (1999)
- "pHi regulatory ion transporters: an update on structure, regulation and cell function", 55, pp.1216~1229 (1999)
- "BCL-2 and MCL-1 expression in Chinese hamster ovary cels inhibits intracellular acidification and apoptosis induced by staurosporine", 225, pp.430~436 (1996)
- "A unique glucose-dependent apoptotic pathway induced by c-Myc", 95, pp.1511~1516 (1998)
- "Role of intra-celular pH in proliferation, transformation, and apoptosis", 29, pp.393~399 (1997)
- "Molecular mechanisms of acidosis-mediated damage", (66), pp.8~14 (1996)
- "Inhibition of apoptosis pulmonary endothelial cels by altered pH", 283, pp.1291~1302 (2002)
- "Increased lactate production follows loss of mitochondrial membrane potential during apoptosis of human leukaemia cells", 114, pp.574~580 (2001)
- "Role of vacuolar adenosine triphosphatase in the regulation of cytosolic pH in hepatocytes", pp.21~34 (1994)
- "atheroprotective effect of laminar fluid shear stres in endothelial cells possible role of mitogen-activated protein kinases", 91, pp.172~176 (2003)
- "Acidosis-induced p38 MAPK activation and its implication in regulation of cardiac contractility", 25, pp.1299~1305 (2004)
- "Advantages of pyruvate over lactate in peritoneal dialysis solutions", 22, pp.385~392 (2001)
- "Ser", Thr protein phosphatase 5 inactivates hypoxia-induced activation of an apoptosis signal-regulating kinase 1, JNK signaling cascade, 2004[DOI]