3 Biological Significance of Manganese in Mammalian Systems

Wedler, Frederick C.

doi:10.1016/s0079-6468(08)70376-x

Cited by 68 publications

(37 citation statements)

References 495 publications

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“…Magnesium also activated the toxins, but to a lesser degree. The activation of hydrolases by manganese has been reported for the E. coli UDP-glucose hydrolase and for certain mammalian hydrolases as well (17,33). A variety of other nucleotide-binding proteins and enzymes also exhibit this in vitro preference for manganese over magnesium (33)(34)(35).…”

Section: Discussionmentioning

confidence: 88%

“…In most instances, the in vivo significance of this result is difficult to ascertain. For example, the intracellular concentration of manganese is usually much less than that of magnesium; however, relative subcellular differences in the concentration of these cations may exist in cells, and, in these instances, regulation by manganese could be physiological relevant (33).…”

Section: Discussionmentioning

confidence: 99%

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Clostridium difficile Toxins A and B Are Cation-dependent UDP-glucose Hydrolases with Differing Catalytic Activities

Ciesla¹,

Bobak²

1998

Journal of Biological Chemistry

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Toxins A and B of Clostridium difficile are UDP-glucose glucosyltransferases that exert their cellular toxicity primarily through their abilities to monoglucosylate, and thereby inactivate, Rho family small GTPases. Toxin A also hydrolyzes UDP-glucose, although this activity is not well characterized. In this study, we measured the kinetics of UDP-glucose hydrolysis by toxins A and B and found significant differences in the catalytic activities of these two structurally homologous toxins. The toxins displayed similar Michaelis constants (K m ) for UDP-glucose, but the maximal velocity (V max ) of toxin B was ϳ5-fold greater than that of toxin A. Toxins A and B exert their enzymatic actions intracellularly, and, interestingly, we found that each toxin absolutely required K ؉ for optimal hydrolase activity; Na ؉ was inactive. The toxins also required certain divalent cations for activity and exhibited a significantly greater V max and lower K m in the presence of Mn 2؉ as compared with Mg 2؉ . We conclude that C. difficile toxins A and B are cation-dependent UDP-glucose hydrolases that differ significantly in their catalytic activities, a finding that may have important implications in understanding their different cytotoxic effects.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Clostridium difficile Toxins A and B Are Cation-dependent UDP-glucose Hydrolases with Differing Catalytic Activities

Ciesla¹,

Bobak²

1998

Journal of Biological Chemistry

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“…1) In contrast, excessive exposure to Mn results in neurotoxicity. 2) Symptoms of acute Mn toxicity are collectively called manganism, and these symptoms are similar to those seen in patients with Parkinson's disease (PD).…”

Section: Introductionmentioning

confidence: 99%

Combined Effects of Manganese, Iron, Copper, and Dopamine on Oxidative DNA Damage

Ando

Ueda

Okamoto

et al. 2011

JOURNAL OF HEALTH SCIENCE

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“…In recent years, much research has focused on Fe, Ru, Os, and, V. These studies have demonstrated that inducing ROS and cell death is a well-known mechanism of bioinorganic complexes [6]. Of all the metals, manganese (Mn), a required cofactor for many ubiquitous enzymes [7], is an essential trace element that plays a central role in the biochemistry and physiology of many living organisms. Simple Mn(II) salts have been reported to exert anti-proliferative effects on several cancer cell lines generally by induction of apoptotic cell death [8].…”

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confidence: 99%

A novel manganese complex LMnAc selectively kills cancer cells by induction of ROS-triggered and mitochondrial-mediated cell death

Zhao

Guo

et al. 2014

Sci. China Life Sci.

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We previously identified a novel synthesized metal compound, LMnAc ([L 2 Mn 2 (Ac)(H 2 O) 2 ](Ac) (L=bis(2-pyridylmethyl) amino-2-propionic acid)). This compound exhibited significant inhibition on cancer cell proliferation and was more selective against cancer cells than was the popular chemotherapeutic reagent cisplatin. In this study, we further investigated the underlying molecular mechanisms of LMnAc-induced cancer cell death. We found that LMnAc achieved its selectivity against cancer cells through the transferrin-transferrin receptor system, which is highly expressed in tumor cells. LMnAc triggered cancer cells to commit autophagy and apoptosis, which was mediated by the mitochondrial pathway. Moreover, LMnAc disrupted mitochondrial function, resulting in mitochondrial membrane potential collapse and ATP reduction. In addition, LMnAc induced intracellular Ca 2+ overload and reactive oxygen species generation. Interestingly, its anticancer effect was significantly reduced following pretreatment with the antioxidant N-acetyl cysteine, indicating that reactive oxygen species triggered cell death. Altogether, our data suggest that LMnAc appears to be a selectively promising anticancer drug candidate. Mn(II) complex, selective, antitumor, autophagy, apoptosis, mitochondria, ROS Citation:Li X, Zhao KD, Guo WJ, Liu X, Liu J, Gao J, Chen QY, Bai YD. A novel manganese complex LMnAc selectively kills cancer cells by induction of ROS-triggered and mitochondrial-mediated cell death. Sci China Life Sci, 2014Sci, , 57: 998 -1010Sci, , doi: 10.1007 Following the landmark discovery of the biological activity of cisplatin [1], metal-based compounds have offered possibilities for the design of therapeutics to study and treat a variety of human diseases. To date, cisplatin remains one of the most effective anticancer drugs in clinical use, while more and more novel metal-based anticancer complexes have been and are being developed [25]. In recent years, much research has focused on Fe, Ru, Os, and, V. These studies have demonstrated that inducing ROS and cell death is a well-known mechanism of bioinorganic complexes [6]. Of all the metals, manganese (Mn), a required cofactor for many ubiquitous enzymes [7], is an essential trace element that plays a central role in the biochemistry and physiology of many living organisms. Simple Mn(II) salts have been reported to exert anti-proliferative effects on several cancer cell lines generally by induction of apoptotic cell death [8]. Moreover, the transport mechanism of Mn(II) in vivo may make Mn(II)-based compounds possible tumor-targets [5,9]. Recently, combining Mn(II) with other functional molecules has become a new strategy for the development of potent anti-tumor compounds. Ligands can significantly alter biological properties by limiting the adverse effects of metal ion overload and facilitate metal ion re-distribution [10]. For example, Mn(II) complexes containing thiosemicarbazone, hydrazone groups or chrysin were reported to have obvious anti-tumor effects [5,11,12].

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3 Biological Significance of Manganese in Mammalian Systems

Cited by 68 publications

References 495 publications

Clostridium difficile Toxins A and B Are Cation-dependent UDP-glucose Hydrolases with Differing Catalytic Activities

Clostridium difficile Toxins A and B Are Cation-dependent UDP-glucose Hydrolases with Differing Catalytic Activities

Combined Effects of Manganese, Iron, Copper, and Dopamine on Oxidative DNA Damage

A novel manganese complex LMnAc selectively kills cancer cells by induction of ROS-triggered and mitochondrial-mediated cell death

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