Bhaskara Vasantha Kumar, Challa Sundaram, Panigrahi Manas, Babu Phanithi Prakash
Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, AP, India.
Neurol India. 2009 May-Jun;57(3):264-8. doi: 10.4103/0028-3886.53265.
Gliomas represent a diverse range of clinical presentation, histological differentiation, and response to therapy. Altered cell proliferation and cell death signals in gliomas are of great interest to elucidate the key molecules involved and to find effective treatment modalities. By considering the role of different proteases in correlation with differential poly (ADP-ribose) polymerase (PARP) fragmentation we have studied the pattern of cell death in human glioma tissues.
In our study, five different human glioma biopsies were collected and analyzed for the PARP cleavage pattern by using western immunoblotting. Samples were also analyzed for pro-caspase 3, calpain I (micro) and II (m), granzyme-B and apoptosis-inducing factor (AIF). Parallel sections of histologically confirmed astrocytoma and glioblastoma multiforme (GBM) were used for immunohistochemical analysis of cleaved caspase-3, granzyme B, AIF and cyclo-oxygenase -2 (cox-2).
We found PARP fragmentation, along with usual approximately 89 kDa and approximately 24 kDa fragments, into other fragments of different molecular weights. Caspase mediated cell death may lead to appearance of larger approximately 89 kDa fragment and smaller approximately 24 kDa fragment indicating existence of apoptosis in the tumors. However, other fragments corresponding to approximately 64 kDa, approximately 54 kDa, and approximately 40 kDa were observed concomitantly in all glial tumor tissues.
These results may indicate, not only apoptosis and necrosis, but there occurs the co-existence of intermediate cell death pathways in human glial tumors.
胶质瘤临床表现多样，组织学分化各异，对治疗的反应也不同。胶质瘤中细胞增殖和细胞死亡信号的改变对于阐明其中涉及的关键分子以及寻找有效的治疗方式具有重要意义。通过考虑不同蛋白酶与差异性聚（ADP - 核糖）聚合酶（PARP）片段化的相关性，我们研究了人类胶质瘤组织中的细胞死亡模式。
在我们的研究中，收集了五例不同的人类胶质瘤活检样本，并通过蛋白质免疫印迹法分析PARP的切割模式。样本还进行了前体半胱天冬酶 - 3、钙蛋白酶I（μ）和II（m）、颗粒酶 - B和凋亡诱导因子（AIF）的分析。组织学确诊的星形细胞瘤和多形性胶质母细胞瘤（GBM）的平行切片用于切割的半胱天冬酶 - 3、颗粒酶B、AIF和环氧化酶 - 2（cox - 2）的免疫组织化学分析。
我们发现PARP片段化，除了通常约89 kDa和约24 kDa的片段外，还形成了其他不同分子量的片段。半胱天冬酶介导的细胞死亡可能导致出现较大的约89 kDa片段和较小的约24 kDa片段，表明肿瘤中存在凋亡。然而，在所有胶质肿瘤组织中同时观察到了对应于约64 kDa、约54 kDa和约40 kDa的其他片段。
这些结果可能表明，人类胶质肿瘤中不仅存在凋亡和坏死，还存在中间细胞死亡途径的共存。
