Effects and Neuro-toxic Mechanisms of 2,2',4,4',5,5'-Hexachlorobiphenyl and Endosulfan in Neuronal Stem Cells.

Abstract

ABSTRACT. Endocrine disrupters are exogenous compounds thought to mimic the action of estrogen or other hormones and influence endocrine activity in the body (Juberg, 2000). These chemicals have adverse effects not only in the reproductive system but also in the central nervous system during development and throughout life. Polychlorinated biphenyls (PCBs) are a class of environmentally persistent and widespread halogenated hydrocarbons. It has been reported that PCBs are potential neurotoxicants. Endosulfan is an organochlorine insecticide that is extensively used to control pests in vegetables, cotton, and fruits. To determine the effect of 2, 2', 4, 4', 5, 5',-hexachlorobiphenyl(2, 4, 5-HCB) and endosulfan on embryo nervous system, we isolated neural stem cells from rat brain at embryonic day 17. Isolated neural stem cells showed pluripotenty. Stem cells could differentiate into neurons and glia. Neurite formation in endosulfan and 2, 4, 5-HCB treated cells. And it appeared to be decreased as compared with that in untreated cells. In order to know the neuro-toxic mechanisms of 2, 4, 5-HCB and endosulfan in neuronal stem cells, we investigated mitogen-activated protein kinase activity (MAPK) and gap junctional intercellular communication (GJIC). Endosulfan decreased the MAPK activity in dose dependent manner. Endosulfan and 2, 4, 5-HCB inhibited GJIC compared to the untreated cell by scrape loading dye transfer (SL/DT). 2, 4, 5-HCB and endosulfan decreased the expression of connexin 43 in dose dependent manner. These results indicated that 2, 4, 5-HCB and endosulfan may inhibit differentiation and proliferation of neural stem cells and gap junctional intercellular communication which play a crucial role in the maintenance of cellular homeostasis. KEY WORDS: endosulfan, gap junctional intercellular communication (GJIC), 2, 2', 4, 4', 5, 5',-hexachlorobiphenyl(2, 4, 5-HCB), mitogenactivated protein kinase (MAPK), neural stem cell.

Endosulfan upregulates AP-1 binding and ARE-mediated transcription via ERK1/2 and p38 activation in HepG2 cells

“…Recent studies on MAPK pathways indicate that in mammalian systems physiologic responses associated with a certain MAPK module can be cell-type specific and dependent on the timing of kinase activation (Schaeffer and Weber, 1999). This might be an explanation for the discrepancy between the results of Kang et al (2001) and other studies including the present study.…”

“…Endosulfan activated the ERK1/2 pathway in the pituitary tumor cell line GH 3 /B6/F10 (Bulayeva and Watson, 2004), in MCF-7 cells (Li et al, 2006), and in human HaCaT keratinocytes (Antherieu et al, 2007; Ledirac et al, 2005). On the contrary, Kang et al (2001) reported endosulfan decreased ERK2 activity in neural stem cells through the inhibition of gap junctional intercellular communication (GJIC) (Kang et al, 2001). Recent studies on MAPK pathways indicate that in mammalian systems physiologic responses associated with a certain MAPK module can be cell-type specific and dependent on the timing of kinase activation (Schaeffer and Weber, 1999).…”

Role of Gap Junctional Intercellular Communication (GJIC) through p38 and ERK1/2 Pathway in the Differentiation of Rat Neuronal Stem Cells

“…Our data suggest that GJIC plays an important role during neuronal stem cell differentiation, and ERK1/2 and p38 MAP kinase signaling pathway may be closely related functionally to regulate gap junction in rat neuronal stem cell-derived cells. Neuronal stem cells are able to differentiate into astrocytes, neurons, and oligodendrocytes [3,10,23], when given the appropriate signals [2,7]. During the stage where the brain develops, gap junctional intercellular communication (GJIC) allows the diffusional exchange of ions and metabolites for communication between neighboring cells [8,14,20].…”

Herbicides and the Risk of Neurodegenerative Disease

“…Endosulfan-treated rats were shown to have increased lipid peroxidation in cerebral tissue, a sign of damaging oxidative stress (Hincal et al, 1995). In vitro studies have shown that endosulfan inhibited proliferation and differentiation of neural stem cells while also inhibiting neurite formation (Kang et al, 2001). Additionally, PC 12 cells incubated with endosulfan were reduced in number, had unusual morphology and exhibited increased apoptosis (Yang et al, 2004).…”