Mishra Sudha, Vinayak Manjula
Biochemistry & Molecular Biology Laboratory, Centre of Advanced Study in Zoology, Banaras Hindu University, Varanasi, 221005, India.
BMC Complement Altern Med. 2015 Aug 15;15:281. doi: 10.1186/s12906-015-0810-5.
Protein kinase C regulates various cellular processes including cell proliferation, cell adhesion, apoptosis, angiogenesis, invasion, and metastasis. Activation of different PKC isozymes results in distinct cellular responses. Novel PKCs are mainly involved in apoptotic process. Atypical PKC subfamily plays a critical role in cell proliferation and apoptosis, cell differentiation and motility. However, Atypical PKCs show contradictory regulation in different tissues or cancer cells. The mechanism of diversified effects is not well explored. Antioxidant ellagic acid shows hepatoprotective, anti-carcinogenic and anti-mutagenic properties. Present study is focused to analyze the effect of ellagic acid on novel and atypical isozymes of PKC in regulation of PKC-mediated apoptosis in liver of lymphoma bearing mice. Implication of ellagic acid treatment to DL mice was analyzed on caspase-3 mediated apoptosis via PKCδ induced activation; and on maintenance of adequate supply of energy during cancer growth.
15-20 weeks old adult DL mice were divided into four groups (n=6). Group 2, 3, 4 were treated with different doses of ellagic acid (40 mg/kg, 60 mg/kg and 80 mg/kg bw). The mice were sacrificed after 19 days of treatment and liver was used for study. The effect of ellagic acid was determined on expression of novel and atypical PKC isozymes. Apoptotic potentiality of ellagic acid was checked on activities of caspase-3 and PKCδ in terms of their catalytic fragments. Aerobic glycolysis was monitored by LDH activity, especially activity of LDH A.
Ellagic acid treatment caused up regulation of expression of almost all novel and atypical PKC isozymes. Activities of PKCδ and caspase-3 were enhanced by ellagic acid, however activities of total LDH and LDH-A were inhibited.
The results show that ellagic acid promotes apoptosis in lymphoma bearing mice via novel and atypical PKCs which involves PKCδ induced caspase-3 activation; and inhibition of glycolytic pathway.
蛋白激酶C调节多种细胞过程，包括细胞增殖、细胞黏附、细胞凋亡、血管生成、侵袭和转移。不同蛋白激酶C同工酶的激活会导致不同的细胞反应。新型蛋白激酶C主要参与细胞凋亡过程。非典型蛋白激酶C亚家族在细胞增殖和凋亡、细胞分化和运动中起关键作用。然而，非典型蛋白激酶C在不同组织或癌细胞中表现出相互矛盾的调节作用。其多样化作用的机制尚未得到充分探索。抗氧化剂鞣花酸具有肝脏保护、抗癌和抗诱变特性。本研究旨在分析鞣花酸对蛋白激酶C的新型和非典型同工酶的影响，以及其在淋巴瘤荷瘤小鼠肝脏中对蛋白激酶C介导的细胞凋亡的调节作用。通过蛋白激酶Cδ诱导的激活，分析鞣花酸处理对DL小鼠半胱天冬酶-3介导的细胞凋亡的影响；以及对癌症生长过程中能量充足供应的维持作用。
将15 - 20周龄的成年DL小鼠分为四组（n = 6）。第2、3、4组用不同剂量的鞣花酸（40 mg/kg、60 mg/kg和80 mg/kg体重）进行处理。处理19天后处死小鼠，取肝脏用于研究。测定鞣花酸对新型和非典型蛋白激酶C同工酶表达的影响。从半胱天冬酶-3和蛋白激酶Cδ的催化片段活性方面检测鞣花酸的凋亡潜力。通过乳酸脱氢酶活性，特别是LDH A的活性监测有氧糖酵解。
鞣花酸处理导致几乎所有新型和非典型蛋白激酶C同工酶的表达上调。鞣花酸增强了蛋白激酶Cδ和半胱天冬酶-3的活性，但抑制了总乳酸脱氢酶和LDH-A的活性。
结果表明，鞣花酸通过新型和非典型蛋白激酶C促进淋巴瘤荷瘤小鼠的细胞凋亡，这涉及蛋白激酶Cδ诱导的半胱天冬酶-3激活；以及对糖酵解途径的抑制。
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