Quercetin protects against aluminium induced oxidative stress and promotes mitochondrial biogenesis via activation of the PGC-1α signaling pathway.
The present investigation was carried out to elucidate a possible molecular mechanism related to the protective effect of quercetin administration against aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of PGC-1α and its downstream targets, i.e. NRF-1, NRF-2 and Tfam in mitochondrial biogenesis. Aluminium lactate (10mg/kg b.wt./day) was administered intragastrically to rats, which were pre-treated with quercetin 6h before aluminium (10mg/kg b.wt./day, intragastrically) for 12 weeks. We found a decrease in ROS levels, mitochondrial DNA oxidation and citrate synthase activity in the hippocampus (HC) and corpus striatum (CS) regions of rat brain treated with quercetin. Besides this an increase in the mRNA levels of the mitochondrial encoded subunits - ND1, ND2, ND3, Cyt b, COX1, COX3 and ATPase6 along with increased expression of nuclear encoded subunits COX4, COX5A and COX5B of electron transport chain (ETC). In quercetin treated group an increase in the mitochondrial DNA copy number and mitochondrial content in both the regions of rat brain was observed. The PGC-1α was up regulated in quercetin treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC-1α. Electron microscopy results revealed a significant decrease in the mitochondrial cross-section area, mitochondrial perimeter length and increase in mitochondrial number in case of quercetin treated rats as compared to aluminium treated ones. Therefore it seems quercetin increases mitochondrial biogenesis and makes it an almost ideal flavanoid to control or limit the damage that has been associated with the defective mitochondrial function seen in many neurodegenerative diseases.
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Deep Raj
DR
Sharma
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Aditya
A
Sunkaria
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Willayat Yousuf
WY
Wani
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Reeta Kumari
RK
Sharma
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Deepika
D
Verma
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India.
Kumari
K
Priyanka
Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Amanjit
A
Bal
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address: kdgill2002@yahoo.co.in.
Kiran Dip
KD
Gill
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000187:drug effects / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004579:Electron Transport / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011794:Quercetin / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors / Q000378:metabolism*
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014157:Transcription Factors; D000080242:8-Hydroxy-2'-Deoxyguanosine; D011794:Quercetin; D000535:Aluminum; D003849:Deoxyguanosine
Aluminium; Electron transport chain; Mitochondrial biogenesis; Neurodegeneration; Quercetin; Reactive oxygen species