Methylmercury inhibits electron transport chain activity and induces cytochrome c release in cerebellum mitochondria

Abstract

-The involvement of oxidative stress has been suggested as a mechanism for toxicity caused by methylmercury (MeHg). One of the major critical sites for oxidative stress is the mitochondria. In this research, to clarify the target site in mitochondria affected by MeHg, the individual activities of the mitochondrial electron transport chain (ETC) (I IV) were examined in the liver, cerebrum and cerebellum of MeHg-intoxicated rats. In addition, to elucidate the mechanism underlying MeHg toxicity, cytochrome c release, caspase 3 activity and histological study were examined in the cerebrum and cerebellum. The cerebellum was found to be an exclusive tissue in which significant MeHg-induced alterations were observed. The complex II activity in the cerebellum mitochondria significantly decreased after MeHg exposure. Cytochrome c release from mitochondria increased only in the cerebellum by MeHg exposure. However, no significant alterations in caspase 3 activity or histological structure were found in brain tissues. These results suggest that MeHg acts on the constituents of complex II in the cerebellum, and induces mitochondrial dysfunction, leading to a release of cytochrome c from mitochondria. These events were considered to occur at the early stage of MeHg intoxication.

RIP1-mediated mitochondrial dysfunction and ROS production contributed to tumor necrosis factor alpha-induced L929 cell necroptosis and autophagy

“…Whether inactivation of caspase-8 or other caspases is involved in these processes remains to be clarified in TNFα-treated L929 cells. Some studies reported that cytochrome c release was a marker of mitochondrial injury [28][29][30]. This was in line with our results that cytochrome c release was accompanied with TNFα administration.…”

Induction by mercury compounds of metallothioneins in mouse tissues: inorganic mercury accumulation is not a dominant factor for metallothionein induction in the liver

“…In the present study we examined accumulations of inorganic mercury and MT inductions in brain, kidney and liver of mice after exposure to sub-lethal doses of Hg(0), Hg(II) and MeHg, and considered the difference in the MT induction processes. Since the cerebellum is known to be more susceptible to MeHg toxicity than the cerebrum (Nakamura et al, 2011;Mori et al, 2007Mori et al, , 2011, responses of these two tissues were separately examined here.…”

Methylmercury induces a brain-specific increase in chemokine CCL4 expression in mice

“…Methylmercury is a pollutant that causes severe central nervous system (CNS) damage (Mori et al, 2011;Watanabe et al, 2009;Yasutake and Nakamura, 2011); however, the mechanism underlying this effect remains unclear. To identify intracellular factors involved in methylmercury-induced CNS damage, we recently used microarray analysis to investigate changes in gene expression change in cerebellum of mice treated with methylmercury, and showed that the expression of multiple genes was induced.…”