Catalase Abstracts 1

© 2011

Towards a "free radical theory of graying": melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage

            (Arck, Overall et al. 2006) Download

Oxidative stress is generated by a multitude of environmental and endogenous challenges such as radiation, inflammation, or psychoemotional stress. It also speeds the aging process. Graying is a prominent but little understood feature of aging. Intriguingly, the continuous melanin synthesis in the growing (anagen) hair follicle generates high oxidative stress. We therefore hypothesize that hair bulb melanocytes are especially susceptible to free radical-induced aging. To test this hypothesis, we subjected human scalp skin anagen hair follicles from graying individuals to macroscopic and immunohistomorphometric analysis and organ culture. We found evidence of melanocyte apoptosis and increased oxidative stress in the pigmentary unit of graying hair follicles. The "common" deletion, a marker mitochondrial DNA-deletion for accumulating oxidative stress damage, occurred most prominently in graying hair follicles. Cultured unpigmented hair follicles grew better than pigmented follicles of the same donors. Finally, cultured pigmented hair follicles exposed to exogenous oxidative stress (hydroquinone) showed increased melanocyte apoptosis in the hair bulb. We conclude that oxidative stress is high in hair follicle melanocytes and leads to their selective premature aging and apoptosis. The graying hair follicle, therefore, offers a unique model system to study oxidative stress and aging and to test antiaging therapeutics in their ability to slow down or even stop this process.

Catalase deficiency and type 2 diabetes

            (Goth 2008) Download

Hereditary catalase deficiencies and increased risk of diabetes

            (Goth and Eaton 2000) Download

Partial or near-total lack of erythrocyte catalase activity is a rare condition, generally thought to be benign. However, little is known of the frequency of common diseases of adult onset in human beings with catalase deficiency. We report that, in a series of Hungarian patients with catalase deficiency, there is a higher frequency of diabetes than in unaffected first-degree relatives and the general Hungarian population. We speculate that quantitative deficiency of catalase might predispose to cumulative oxidant damage of pancreatic beta-cells and diabetes.

Catalase deficiency, diabetes, and mitochondrial function

            (Heales 2001) Download

Mammalian catalase: a venerable enzyme with new mysteries

            (Kirkman and Gaetani 2007) Download

Mammalian catalase has been the subject of many classic biochemical studies. Despite our detailed knowledge of its functional mechanisms and its three-dimensional structure, however, several unexpected features of mammalian catalase have been recently discovered. For example, some mammalian catalases seem to have oxidase activity and produce reactive oxygen species when exposed to UVB light. In addition, bovine catalase uses unbound NAD(P)H to prevent substrate inactivation without displacing catalase-bound NADP(+). Coupled with the earlier discovery of catalase-bound NADPH, these developments indicate that serendipity and new investigative approaches can reveal unexpected features, even for an enzyme that has been studied for over 100 years.

Correlation of H2O2 production and liver catalase during riboflavin deficiency and repletion in mammals

            (Lee, Ye et al. 1983) Download

A substantial decrease in liver peroxisomal catalase was found during riboflavin deficiency in rats. This decrease is greater than that found among other hemoproteins and seems to follow decrease in flavin-dependent peroxisomal oxidases. This is not due to a general depression of peroxisomal enzymes, since Cu-dependent urate oxidase activity was not changed. Furthermore, the level of catalase activity as well as flavin-dependent oxidases was restored by riboflavin repletion. These results suggest that hydrogen peroxide, the substrate for catalase produced by several flavoprotein oxidases, induces catalase in mammals as has been indicated for certain bacteria.


Telomerase deficiency promotes oxidative stress by reducing catalase activity

            (Perez-Rivero, Ruiz-Torres et al. 2008) Download

Telomere shortening and redox imbalance have been related to the aging process. We used cultured mouse embryonic fibroblasts (MEF) isolated from mice lacking telomerase activity (Terc(-/-)) to analyze the redox balance and the functional consequences promoted by telomerase deficiency. Comparison with wild-type (WT) MEF showed that Terc(-/-) MEF had greater oxidant damage, showing higher superoxide anion and hydrogen peroxide production and lower catalase activity. Restoration of telomerase activity in Terc(-/-) MEF increased catalase expression and activity. TGF-beta1 and collagen type IV levels were higher in Terc(-/-) than in WT MEF. TGF-beta1 promoter activity decreased when Terc(-/-) MEF were incubated with exogenous catalase, suggesting that catalase deficiency is the cause of the TGF-beta1 increase. Similar results were obtained in vivo. Homogenized renal cortex from 6-month-old Terc(-/-) showed higher oxidant capacity, lower catalase activity, greater oxidative damage, and higher TGF-beta1 and fibronectin levels than that from WT mice. In summary, telomerase deficiency reduces catalase activity, determining a redox imbalance that promotes overexpression of TGF-beta1 and extracellular matrix proteins.

Methionine sulfoxide reductases A and B are deactivated by hydrogen peroxide (H2O2) in the epidermis of patients with vitiligo

            (Schallreuter, Rubsam et al. 2008) Download

Patients with the depigmentation disorder vitiligo have low catalase expression/activities and constantly accumulate 10(-3) M hydrogen peroxide (H(2)O(2)) in their skin. Such high concentrations of H(2)O(2) oxidize L-methionine residues in proteins and peptides to (R and S)-methionine sulfoxide diasteriomers. In vivo FT-Raman Spectroscopy revealed the presence of methionine sulfoxide in the depigmented skin of patients with active vitiligo. In normal healthy human skin, methionine sulfoxide reductases A and B specifically reduce methionine sulfoxides (S) and (R), respectively, back to L-methionine consequently repairing oxidatively damaged proteins and peptides. In this report, we show that the expression/activities of MSRA and MSRB are significantly decreased in the epidermis of patients with vitiligo compared to healthy controls. Also, we used recombinant human MSRA and MSRB1 to show that both enzymes are deactivated by 10(-3) M H(2)O(2) by 85 and 40%, respectively. Structural modelling based on the crystal structure of human MSRA revealed that the active site of this enzyme is significantly altered after H(2)O(2)-mediated oxidation of L-methionine, L-tryptophan, and L-cysteine residues in its active site. Taken together, our results confirm that very important anti-oxidant enzymes are seriously affected in acute vitiligo.


Peroxisomes and aging

            (Terlecky, Koepke et al. 2006) Download

Peroxisomes are indispensable for proper functioning of human cells. They efficiently compartmentalize enzymes responsible for a number of metabolic processes, including the absolutely essential beta-oxidation of specific fatty acid chains. These and other oxidative reactions produce hydrogen peroxide, which is, in most instances, immediately processed in situ to water and oxygen. The responsible peroxidase is the heme-containing tetrameric enzyme, catalase. What has emerged in recent years is that there are circumstances in which the tightly regulated balance of hydrogen peroxide producing and degrading activities in peroxisomes is upset-leading to the net production and accumulation of hydrogen peroxide and downstream reactive oxygen species. The factor most essentially involved is catalase, which is missorted in aging, missing or present at reduced levels in certain disease states, and inactivated in response to exposure to specific xenobiotics. The overall goal of this review is to summarize the molecular events associated with the development and advancement of peroxisomal hypocatalasemia and to describe its effects on cells. In addition, results of recent efforts to increase levels of peroxisomal catalase and restore oxidative balance in cells will be discussed.

Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair

            (Wood, Decker et al. 2009) Download

Senile graying of human hair has been the subject of intense research since ancient times. Reactive oxygen species have been implicated in hair follicle melanocyte apoptosis and DNA damage. Here we show for the first time by FT-Raman spectroscopy in vivo that human gray/white scalp hair shafts accumulate hydrogen peroxide (H(2)O(2)) in millimolar concentrations. Moreover, we demonstrate almost absent catalase and methionine sulfoxide reductase A and B protein expression via immunofluorescence and Western blot in association with a functional loss of methionine sulfoxide (Met-S=O) repair in the entire gray hair follicle. Accordingly, Met-S=O formation of Met residues, including Met 374 in the active site of tyrosinase, the key enzyme in melanogenesis, limits enzyme functionality, as evidenced by FT-Raman spectroscopy, computer simulation, and enzyme kinetics, which leads to gradual loss of hair color. Notably, under in vitro conditions, Met oxidation can be prevented by L-methionine. In summary, our data feed the long-voiced, but insufficiently proven, concept of H(2)O(2)-induced oxidative damage in the entire human hair follicle, inclusive of the hair shaft, as a key element in senile hair graying, which does not exclusively affect follicle melanocytes. This new insight could open new strategies for intervention and reversal of the hair graying process.


Evolution of catalases from bacteria to humans

            (Zamocky, Furtmuller et al. 2008) Download

Excessive hydrogen peroxide is harmful for almost all cell components, so its rapid and efficient removal is of essential importance for aerobically living organisms. Conversely, hydrogen peroxide acts as a second messenger in signal-transduction pathways. H(2)O(2) is degraded by peroxidases and catalases, the latter being able both to reduce H(2)O(2) to water and to oxidize it to molecular oxygen. Nature has evolved three protein families that are able to catalyze this dismutation at reasonable rates. Two of the protein families are heme enzymes: typical catalases and catalase-peroxidases. Typical catalases comprise the most abundant group found in Eubacteria, Archaeabacteria, Protista, Fungi, Plantae, and Animalia, whereas catalase-peroxidases are not found in plants and animals and exhibit both catalatic and peroxidatic activities. The third group is a minor bacterial protein family with a dimanganese active site called manganese catalases. Although catalyzing the same reaction (2 H(2)O(2)--> 2 H(2)O+ O(2)), the three groups differ significantly in their overall and active-site architecture and the mechanism of reaction. Here, we present an overview of the distribution, phylogeny, structure, and function of these enzymes. Additionally, we report about their physiologic role, response to oxidative stress, and about diseases related to catalase deficiency in humans.




References

Arck, P. C., R. Overall, et al. (2006). "Towards a "free radical theory of graying": melanocyte apoptosis in the aging human hair follicle is an indicator of oxidative stress induced tissue damage." FASEB J 20(9): 1567-9.

Goth, L. (2008). "Catalase deficiency and type 2 diabetes." Diabetes Care 31(12): e93.

Goth, L. and J. W. Eaton (2000). "Hereditary catalase deficiencies and increased risk of diabetes." Lancet 356(9244): 1820-1.

Heales, S. J. (2001). "Catalase deficiency, diabetes, and mitochondrial function." Lancet 357(9252): 314.

Kirkman, H. N. and G. F. Gaetani (2007). "Mammalian catalase: a venerable enzyme with new mysteries." Trends Biochem Sci 32(1): 44-50.

Lee, S. S., J. H. Ye, et al. (1983). "Correlation of H2O2 production and liver catalase during riboflavin deficiency and repletion in mammals." Biochem Biophys Res Commun 117(3): 788-93.

Perez-Rivero, G., M. P. Ruiz-Torres, et al. (2008). "Telomerase deficiency promotes oxidative stress by reducing catalase activity." Free Radic Biol Med 45(9): 1243-51.

Schallreuter, K. U., K. Rubsam, et al. (2008). "Methionine sulfoxide reductases A and B are deactivated by hydrogen peroxide (H2O2) in the epidermis of patients with vitiligo." J Invest Dermatol 128(4): 808-15.

Terlecky, S. R., J. I. Koepke, et al. (2006). "Peroxisomes and aging." Biochim Biophys Acta 1763(12): 1749-54.

Wood, J. M., H. Decker, et al. (2009). "Senile hair graying: H2O2-mediated oxidative stress affects human hair color by blunting methionine sulfoxide repair." FASEB J 23(7): 2065-75.

Zamocky, M., P. G. Furtmuller, et al. (2008). "Evolution of catalases from bacteria to humans." Antioxid Redox Signal 10(9): 1527-48.