Curcumin enhances paraquat-induced apoptosis of N27 mesencephalic cells via the generation of reactive oxygen species

Abstract

Curcumin, the active compound of the rhizome of Curcuma longa has anti-inflammatory, antioxidant and antiproliferative activities. This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. While curcumin has been identified as an activator of apopotosis in several cell lines, the mechanism by which it initiates apoptosis, however, remains poorly understood. We considered curcumin from the point of view of its ability to protect against oxidative stress, the latter being one factor strongly implicated in the development of Parkinson’s disease. Althougth the etiology of Parkinson’s disease remains unknown, epidemiological studies have linked exposure to pesticides such paraquat to an increased risk of developing the condition. Analysis of the neurotoxic properties of these pesticide compounds has been focused on their ability to induce oxidative stress in neural cells. Given curcumin’s capacity to protect against oxidative stress, it has been considered as a potential therapeutic agent for neurodegenerative diseases such as Parkinson’s disease that involve an oxidative stress component. In the present report we describe the effect of curcumin in paraquat-mediated apoptosis of N27 mesencepahlic cells. We show that subtoxic concentrations of curcumin sensitize N27 mesencephalic cells to paraquat-mediated apoptosis.

Nitric oxide in paraquat‐mediated toxicity: A review

“…Although the role of PQ treatment in eNOS expression has not been extensively studied, PQ exposure has been shown to upregulate eNOS mRNA in bovine aortic endothelial cells [30], suggesting a mechanism of regulation of eNOS expression that is dependent on oxidative stress generated by PQ exposure. However, PQ exposure to SH-SY5Y cells does not modulate the expression of eNOS after 24 h of exposure [25], indicating that the putative role of PQ in eNOS expression needs further evaluation. Changes in nNOS expression have been shown in response to stressful conditions; however, such changes after PQ exposure are less well documented.…”

“…iNOS mRNA is upregulated in vivo in rodents after administered PQ reaches significant levels in liver tissues, whereas kidney and lung tissues show little change [22,23]. Polymorphonuclear leukocytes (PMNs) isolated from rats exposed to PQ [24] and immortalized mesencephalic cells [25] also express iNOS. Human lung epithelial cells treated with PQ also express significant amounts of iNOS mRNA [23].…”

“…The herbicide PQ has been repeatedly suggested as a candidate environmental agricultural chemical risk factor owing [51] Lung toxicity Human N/A Beneficial Eisenman et al [53] Lung toxicity Human N/A Beneficial Maruyama et al [54] Lung toxicity Human N/A Beneficial Midorikawa and Ogata [55] Lung toxicity Rodent N/A Beneficial Cho et al [56] Lung toxicity Rodent N/A Beneficial Yeh et al [23] Lung toxicity Human Lung epithelial cells Beneficial Yeh et al [23] Lung toxicity Rodent Lung epithelial cells Beneficial Mustafa et al [59] Lung toxicity Rodent N/A Harmful Berisha et al [60] Lung toxicity Rodent Isolated Guinea Pigs Lungs Harmful Djukic et al [77] Neurotoxicity Rodent Striatum of Wistar rats Harmful Shimizu et al [78] Neurotoxicity Rodent N/A Harmful Ortiz-Ortiz et al [25] Neurotoxicity Human SH-SY5Y Harmful to its structural similarity to MPP+ (1-methyl-4-phenylpyridinium ion), the active component of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a synthetic heroin compound demonstrated to produce a Parkinsonian-syndrome in humans following inadvertent exposure [68]. However, although epidemiological studies have linked the development of PD with PQ exposure [42,63,65,69,70], the role of PQ in the development of PD is still under debate, mainly because investigators have not been able to definitively determine whether PQ is able to cross the blood-brain barrier.…”

“…SH-SY5Y cells coexpressed the three isoforms of NOS, and the expression of iNOS increased significantly after PQ exposure. Thus, PQ toxicity is characterized by the production of toxic levels of NO, O 2 production and thus, apoptotic cell death [25].…”

Combining Curcumin (Diferuloylmethane) and Heat Shock Protein Inhibition for Neurofibromatosis 2 Treatment: Analysis of Response and Resistance Pathways

“…Curcumin increases the levels of reactive oxygen species (ROS) in several tumor cell lines, especially hose sensitive to curcumin-induced apoptosis (15,40,41). tInduction of ROS, in turn, is associated with the upregulation of hsp70 (15).…”