G0/G1 Phase Arrest and Apoptosis Induced by Manganese Chloride on Cultured Rat Astrocytes and Protective Effects of Riluzole

Abstract

Occupational or environmental exposure to excessive Mn would cause manganism, which is resembled Parkinson disease. However, the mechanism underlying manganism is still unknown. It had been documented that astrocytes play important roles in physiological function in brain. Therefore, in the present study, the cultured astrocytes were exposed to 0, 125, 250, and 500 μM MnCl(2), and cell viability, lactate dehydrogenase (LDH) leakage, morphological change, cell cycle progression, and apoptosis were determined. In addition, 100 μM riluzole (a glutamatergic modulator) was pretreated for 6 h before no MnCl(2) exposure or 500 μM MnCl(2) exposure. The results showed that cell viability inhibited, LDH leakage elevated, morphology injured, G(0)/G(1) phase cell cycle arrested, and apoptosis rate increased in a concentration-dependent manner. Further investigation indicated that riluzole pretreatment reversed cytotoxicity, cell cycle aberration, and apoptosis on astrocytes caused by MnCl(2). These results suggested that MnCl(2) could cause cytotoxicity, cell cycle arrest, and apoptosis concentration-dependently; riluzole might antagonize Mn toxicity on astrocytes.

Anti-aging effects of deuterium depletion on Mn-induced toxicity in a C. elegans model

“…This can be suggested because the absence of this caspase caused a loss of the Mn toxic effect. In fact, apoptosis has been associated to Mn toxicity in cultured neuronal cells (Deng et al, 2011; Yoon et al, 2011). Similarly, the double mutant ced-3;ced-9 also has shown the same effect as the single mutant ced-3.…”

DNA Damage Induced by Manganese

“…71 MnCl 2 has been reported to cause G(0)/G(1) phase cell cycle arrest and S phase arrest in cultured rat astrocytes and A549 cells. 72,73 Moreover, in PC12-derived neurons, MnCl 2 increased the population of cells in the G2/M phase, but reduced the population of cells in the S phase, leading to a significant increase in the G2/S ratio. 74 The consequence of these observed arrests might be persistence of DNA damage.…”

Manganese Inhibits Viability of Prostate Cancer Cells

“…Studies on PC12 cells derived from the adrenal gland in rats, showed that Mn induces DNA fragmentation, a characteristic marker of apoptosis (7). Deng et al showed that Mn exposure of cultured astrocytes from rats inhibits cell viability, elevates the level of lactate dehydrogenase (LDH) leakage, and induces G 0 /G 1 phase arrest and apoptosis (8). Studies on the arthropod Nephrops norvegicus have demonstrated that an excess of Mn inhibits proliferation of hematopoietic stem cells and induces apoptosis of these precursor cells (9).…”