TY - JOUR
T1 - Studies on genomic DNA topology and stability in brain regions of Parkinson's disease
AU - Hegde, Muralidhar L.
AU - Gupta, Veer Bala
AU - Anitha, M.
AU - Harikrishna, T.
AU - Shankar, S. K.
AU - Muthane, Uday
AU - Subba Rao, K.
AU - Jagannatha Rao, K. S.
N1 - Funding Information:
The authors thank Director, CFTRI for his encouragement. We thank Chairman, Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India, for providing facilities for Circular Dichroism study. The financial support by Department of Biotechnology, India, through Indo-Israel Joint Project on Human Genome is gratefully acknowledged. We acknowledge Human Brain Tissue Repository for Neurobiological Studies (Human Brain Bank), Department of Neuropathology, NIMHANS, Bangalore, for providing human brain tissue. M.L.H. is thankful to Council for Scientific and Industrial Research (CSIR), India, for Senior Research Fellowship. V.B.G. thanks Indian Council for medical Research (ICMR) for Senior research fellowship.
PY - 2006/5/15
Y1 - 2006/5/15
N2 - DNA damage has been postulated as a mechanism of neuronal death in Parkinson's disease (PD). In the present study, genomic DNA was isolated from eight brain regions (frontal, temporal, and occipital cortex, hippocampus, caudate/putamen, thalamus, cerebellum, and midbrain) from five neuropathologically confirmed cases of Parkinson's disease and six control brains and analyzed for the presence of single and double strand breaks, melting temperature, EtBr intercalation, DNAse digestion pattern, and DNA conformations. The results showed that DNA from midbrain in PD accumulated significantly higher number of strand breaks than age-matched controls. Caudate nucleus/putamen, thalamus, and hippocampus also showed more DNA fragmentation compared to control brains. Circular dichroism studies showed that DNA conformation was altered with imprecise base stacking in midbrain, caudate nucleus/putamen, thalamus, and hippocampus in PD. However, DNA from frontal, temporal, and occipital cortex, and cerebellum was not affected significantly in PD group as compared to controls. This study provides a comprehensive database on stability, damage, and conformations of DNA in different regions in brains of PD patients.
AB - DNA damage has been postulated as a mechanism of neuronal death in Parkinson's disease (PD). In the present study, genomic DNA was isolated from eight brain regions (frontal, temporal, and occipital cortex, hippocampus, caudate/putamen, thalamus, cerebellum, and midbrain) from five neuropathologically confirmed cases of Parkinson's disease and six control brains and analyzed for the presence of single and double strand breaks, melting temperature, EtBr intercalation, DNAse digestion pattern, and DNA conformations. The results showed that DNA from midbrain in PD accumulated significantly higher number of strand breaks than age-matched controls. Caudate nucleus/putamen, thalamus, and hippocampus also showed more DNA fragmentation compared to control brains. Circular dichroism studies showed that DNA conformation was altered with imprecise base stacking in midbrain, caudate nucleus/putamen, thalamus, and hippocampus in PD. However, DNA from frontal, temporal, and occipital cortex, and cerebellum was not affected significantly in PD group as compared to controls. This study provides a comprehensive database on stability, damage, and conformations of DNA in different regions in brains of PD patients.
KW - Apoptosis/necrosis
KW - DNA conformation
KW - DNA fragmentation
KW - DNA stability
KW - Midbrain
KW - Parkinson's disease
KW - Strand breaks
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U2 - 10.1016/j.abb.2006.02.018
DO - 10.1016/j.abb.2006.02.018
M3 - Article
C2 - 16600170
AN - SCOPUS:33646136465
SN - 0003-9861
VL - 449
SP - 143
EP - 156
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 1-2
ER -