Galactose toxicity in animals

Lai, Kent; Elsas, Louis J.; Wierenga, Klaas J.

doi:10.1002/iub.262

Cited by 115 publications

(106 citation statements)

References 196 publications

(160 reference statements)

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“…GALE protein is an enzyme responsible for the epimerization of UDP-glucose and UDP-N-acetyl glucosamine to UDP-galactose, and UDP-N-acetyl galactosamine, and vice versa (Niou et al, 2009;Bang et al, 2009). GALE plays crucial role in energy metabolism through production of UDP-glucose and UDP-N-acetyl glucosamine necessary for mucopolysaccharide, glycoprotein, glycolipid, and the proteoglycan biosynthesis (Sweeney et al, 1993;Lai et al, 2009). The mechanism involved in the pathogenesis of naturally occurring TD is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Effect of thiram on avian growth plate chondrocytes in culture

Rasaputra

Liyanage²,

Lay³

et al. 2013

J. Toxicol. Sci.

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-Thiram is a dithiocarbamate pesticide that causes tibial dyschondroplasia (TD), a growth plate defect, in poultry. Deaths of transitional zone chondrocytes appear to interrupt endochondral bone development leading to the broadening of growth plate. The mechanism of action of thiram on chondrocytes is not well understood. Since proteins play major roles in different aspects of cell's metabolism, growth, and survival, the objective of this study was to find whether thiram produces proteomic changes that could impair the development of chondrocytes. The chondrocytes, isolated from proximal tibial growth plates, were cultured with or without a sub-lethal concentration of thiram for 48 hr, and the cell proteins were extracted, and subjected to 2-D gel electrophoresis. The gel images were compared and statistically evaluated using Melanie software to identify differentially expressed protein spots. Of a total of 72 identifiable spots 3 were down-regulated and 2 up-regulated in thiram treated chondrocytes. In-gel trypsin digestion of the protein spots followed by their characterization by matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry identified 25 spots comprising of 23 proteins. Two of 3 down-regulated proteins were identified as a heat shock protein 70 (HSP 70) and a GALE (UDP-galactose-4 epimerase) protein isoform I. The up-regulated proteins were Serpin H1, a protein involved in collagen metabolism and a redox sensor NmrA-like (NMRAL) family domain protein-1. Both GALE and NMRAL proteins are implicated in energy metabolism and redox regulation whereas the HSP 70 protects cells against stress, and implicated in chondrocyte hypertrophy, an important event in endochondral bone formation. The failure of chondrocyte protective mechanisms such as associated with protection against cellular stress and energy metabolism appear to be the likely cause for chondrocyte death induced by thiram.

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Section: Discussionmentioning

confidence: 99%

Effect of thiram on avian growth plate chondrocytes in culture

Rasaputra

Liyanage²,

Lay³

et al. 2013

J. Toxicol. Sci.

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“…Inherited deficiencies of GALK, GALT, and GALE activities in humans have all been observed, studied, and reviewed extensively (Bosch et al, 2002;Elsas 1993;Fridovich-Keil et al, 1993a). The clinical manifestations of each enzyme deficiency, however, differ markedly Berry and Elsas, 2011;Fridovich-Keil et al, 1993a;Lai et al, 2009;). For instance, patients with GALK deficiency (MIM 230200) (Type II Galactosemia) have the mildest clinical consequences, as they may present only with cataracts (Bosch et al, 2002).…”

Section: What Is Galactosemia?mentioning

confidence: 99%

“…Unlike Type II or the peripheral Type III Galactosemia, patients with Type I (GALTdeficiency) Galactosemia, also the most common type of Galactosemia, suffer a range of debilitating long-term complications, which include premature ovarian insufficiency, learning deficits, ataxia and speech dyspraxia (Lai et al, 2009;Berry and Elsas, 2011). The current galactose-restricted diet fails to prevent these complications, and the medical/ patient communities are yearning for a more effective therapy.…”

Section: The Issuesmentioning

confidence: 99%

Use of Site-Directed Mutagenesis in the Diagnosis, Prognosis and Treatment of Galactosemia

Tang¹,

Wierenga²,

Lai³

2013

Genetic Manipulation of DNA and Protein - Examples From Current Research

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“…Glukozun epimerizasyonu sonucu oluşabilen galaktoz insülinden bağımsız ola-DOI: 10.5455/musbed.20140103081933 rak hücre içerisine alınır. Oluşan sakkaritlerin hücre membranında bulunan lipit ve proteinlerle bağlanmaları sonucu glikozaminoglikanlar, glikoproteinler ve glikolipidler oluşur (1). Farelere düşük dozda D-galaktoz enjeksiyonun hız-landırılmış yaşlanmaya benzeyen belirtileri ilk kez Çin'de bildirilmiştir.…”

Section: Introductionunclassified

Evaluation of Tissue Factor Activities and Sialic Acid Levels in D-Galactose Induced Aging Model

Stundag¹,

Oktay²,

Emekli-Alturfan³

et al. 2014

MUSBED

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D-galaktoz ile oluşturulmuş yaşlanma modelinde doku faktörü aktivitesinin ve sialik asit miktarının değerlendirilmesi Amaç: Bu çalışmada D-galaktoz ile yaşlandırılmış, doğal yaşlı ve kontrol grubu sıçanların karaciğer ve renal dokularının doku faktörü (TF) aktivitelerinin ve inflamatuvar hastalıklar için değerli bir indikatör olan sialik asit (SA) miktarlarının ölçülmesi amaçlandı. Yöntemler: Çalışmada yirmi haftalık 28 adet Sprague-Dawley erkek rat kullanıldı. Gruplar; 1) genç kontrol grubu (n= 8), 2) doğal yaşlı erkek grup (n= 10), 3) 6 hafta süreyle 60 mg/kg/gün i.p. D-galaktoz enjekte edilen D-galaktoz ile yaşlandırılmış grup (n= 10) şeklinde oluşturuldu. İşlemler sonunda, ratlar bir gece aç bırakılarak sakrifiye edildi ve homojenizasyon için böbrek ve karaciğer dokuları toplandı. TF aktivitesi Quick metoduna, SA miktarı ise Warren'ın metoduna göre ölçüldü. Bulgular: D-galaktoz grubu böbrek dokusunda SA miktarı kontrol ve doğal yaşlı gruplara oranla anlamlı derecede azalmış, TF aktivitesi ise anlamlı derecede artmıştır. Karaciğer dokusu SA miktarında gruplar arasında anlamlı bir değişiklik gözlenmemiştir. Karaciğer TF aktivitesi ise D-galaktoz grubunda kontrol grubuna göre artmıştır. Sonuç: D-galaktoz ile oluşturulan yaşlanma modelinde böbrek ve karaciğer dokularında meydana gelen TF aktivitesi artışı ve böbrek SA seviyelerindeki azalma D-galaktozun yaşlanma ile ilgili tromboz/hemostaz çalışmalarında kullananılabileceğini göstermektedir. Anahtar sözcükler: D-galaktoz, yaşlanma, doku faktörü, sialik asit ABS TRACT Evaluation of tissue factor activities and sialic acid levels in D-galactose induced aging modelObjective: The aims of this study are to evaluate the changes in tissue factor (TF) activities and sialic acid (SA) concentrations of D-galactose induced rat hepatic and renal tissues and compare with the naturally aged and the control groups. Methods: In this study Sprague-Dawley male rats (n=28, 20 weeks old) were used. The experiment and the control groups were organized as follows: 1) young male control group (n= 8, 20 weeks old). 2) naturally aged male group (n= 10) 3) D-Galactose induced ageing group (D-galactose injected (60 mg/kg/day) for 6 weeks, n= 8, 20-week-old). At the end of the treatment, the rats were sacrificed following an overnight fast, kidney and liver tissues were immediately collected for homogenization. TF activity and SA levels were measured by the methods of Quick and Warren respectively. Results: SA levels of kidney decreased whereas TFa (TF activity) increased significantly in the D-galactose induced aging group when compared with the control and the naturally aged groups. SA levels of liver did not change significantly between the groups. TFa of liver increased significantly compared with the control group. Conclusion: Increased TFa (TF activity) of kidney and liver and decreased SA levels of kidney in D-galactose induced aging model show that this model can be used in studies related with aging, thrombosis and haemostasis.

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Galactose toxicity in animals

Cited by 115 publications

References 196 publications

Effect of thiram on avian growth plate chondrocytes in culture

Effect of thiram on avian growth plate chondrocytes in culture

Use of Site-Directed Mutagenesis in the Diagnosis, Prognosis and Treatment of Galactosemia

Evaluation of Tissue Factor Activities and Sialic Acid Levels in D-Galactose Induced Aging Model

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