Dehydroepiandrosterone protects bovine retinal capillary pericytes against glucose toxicity

Brignardello, Enrico; Beltramo, Elena; Molinatti, P. A.; Aragno, Manuela; Gatto, V; Tamagno, Elena; Danni, Oliviero; Porta, Massimo; Boccuzzi, Giuseppe

doi:10.1677/joe.0.1580021

Cited by 47 publications

(47 citation statements)

References 36 publications

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“…Loss of retinal capillary pericytes, a characteristic change in the early phase of diabetic retionopathy, is considered a key step in retinopathy progression [20]. Brignardello et al [21] demonstrated that by its antioxidant properties, dehydroepiandrosterone (DHEA), which is a weak androgen that contributes to androgenicity mainly after peripheral convesion to testosterone, prevents suppression of retinal capillary pericyte growth caused by excessive glucose.…”

Section: Discussionmentioning

confidence: 99%

Low Serum Testosterone Concentration in Middle-aged Men with Type 2 Diabetes

et al. 2007

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Abstract. Low concentrations of endogenous androgens have been linked with insulin resistance and atherosclerosis. Men with diabetes have been reported to have lower serum testosterone concentration than non-diabetic men; however, there has never been a large study. The aim of this study was to investigate if endogenous androgen concentration is certainly lower in a relatively large number of Japanese patients with type 2 diabetes compared with healthy men, and to identify what factors may be associated with low serum testosterone concentrations in men with type 2 diabetes. Serum free testosterone concentrations were measured in 524 healthy men and in 331 consecutive Japanese men with type 2 diabetes between 40 and 69 years old. In addition, we investigated the relationships between serum free testosterone concentration and luteinizing hormone (LH) concentration as well as major cardiovascular risk factors including age, blood pressure, plasma lipid concentration, glycemic control (HbA 1c ), and BMI. Serum free testosterone concentrations were lower in men with type 2 diabetes than in healthy men in the 40-49 years group (10.9 ± 3.3 vs. 14.0 ± 3.6 pg/ml, P<0.0001), in the 50-59 years group (10.4 ± 3.2 vs. 12.1 ± 2.9 pg/ml, P<0.0001), and in the 60-69 years group (9.5 ± 2.6 vs. 10.5 ± 2.9 pg/ml, P = 0.0104). A negative correlation was found between serum free testosterone and LH concentrations (r = -0.326, P<0.0001). In conclusion, serum free testosterone concentration is certainly lower in a relatively large number of Japanese patients with type 2 diabetes compared with healthy men with each decade of life between 40 and 69 years old.

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Section: Discussionmentioning

confidence: 99%

Low Serum Testosterone Concentration in Middle-aged Men with Type 2 Diabetes

et al. 2007

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“…Bovine retinal pericytes (BRP) were obtained from pools of 15 to 20 bovine retinas, with a partial modification of two precedent methods [15,16,17]. BRP were characterized by 3G5 (a specific membrane ganglioside) fluorescence immunostaining [17] and were grown in DMEM 5.6 mmol/l glucose with 20% FCS in primary cultures and 10% FCS in secondary cultures.…”

Section: Methodsmentioning

confidence: 99%

“…BRP were characterized by 3G5 (a specific membrane ganglioside) fluorescence immunostaining [17] and were grown in DMEM 5.6 mmol/l glucose with 20% FCS in primary cultures and 10% FCS in secondary cultures.…”

Section: Methodsmentioning

confidence: 99%

A study of capillary pericyte viability on extracellular matrix produced by endothelial cells in high glucose

et al. 2003

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Aims/hypothesis. Thickening of the basement membrane and selective loss of pericytes occur early in diabetic retinopathy. As we showed previously that pericyte adhesion is impaired on extracellular matrix produced by endothelial cells in high hexose concentrations, we aimed to verify if altered adhesion could influence pericyte viability and replication. Methods. Conditioned extracellular matrices were obtained by growing human umbilical vein endothelial cells in media containing 28 mmol/l D-glucose, with or without the inhibitors of protein glycation thiamine or aminoguanidine, and D-galactose or L-glucose up to 28 mmol/l. Having removed the endothelium, bovine retinal pericytes were grown on these matrices and, in separate experiments, on laminin, fibronectin or type IV collagen. Pericyte viability and replication were measured by cell counts and DNA synthesis after 7 days, cell cycle traversal after 2 days and apoptosis after 18 h, 2 days and 7 days.Results. Pericyte counts and DNA synthesis were reduced on matrices produced in high D-glucose and Dgalactose, whilst matrix obtained in L-glucose reduced DNA synthesis but not counts. Both thiamine and aminoguanidine corrected reduced pericyte viability when added to high D-glucose. Cell cycle and apoptosis were not affected by growing pericytes on different conditioned matrices. Laminin, fibronectin and type IV collagen did not modify pericyte replication. Conclusions/interpretations. Reduced pericyte counts could depend on impaired initial adhesion to the extracellular matrix produced by endothelium in high hexose concentrations, rather than impaired replication or viability. Altered cell-matrix interactions might facilitate pericyte dropout in diabetic retinopathy, independently of the effects of high glucose on pericyte replication. [Diabetologia (2003) 46:409-415] Keywords Diabetic retinopathy, extracellular matrix, pericytes, endothelium, glucose, galactose, aminoguanidine, thiamine, glycation. and is observed in other forms of hyperhexosaemia, such as galactose-fed rats, which also develop a diabetic-like retinopathy [3,4]. The evolution of diabetic retinopathy is strongly influenced by qualitative and quantitative changes in the extracellular matrix (ECM) of the capillary basement membrane. In particular, alterations of some ECM components were shown to influence the characteristics of endothelium [5] and ECM-associated growth factors [6], although the mechanisms are still unclear.Endothelium is likely to represent the major contributor to the synthesis of capillary ECM material. In particular, endothelial cells were found to increase their synthesis of type IV collagen and fibronectin Thickening of the basement membrane is an early event in the course of diabetic microangiopathy [1,2]

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“…These wide-ranging activities cannot fully be explained by activation of the androgen or estrogen receptors. Published data support the hypothesis that DHEA acts to limit lipid peroxidation, in vivo as well as in vitro (17)(18)(19)(20)(21)(22)(23). Since many of the diseases on which DHEA has a beneficial effect have been related to repeated oxidative insult (24), the antioxidant properties of DHEA might be expected to explain its effects.…”

Section: Introductionmentioning

confidence: 62%

“…At these concentrations, DHEA has been reported to protect both bovine retinal capillary pericytes against glucose toxicity (23) and human low density lipoproteins (LDL) against peroxidation induced by g radiolysis of ethanol-water mixtures (22).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line

Gallo

Aragno

Gatto

et al. 1999

European Journal of Endocrinology

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Objective: Dehydroepiandrosterone (DHEA) is a widely studied steroid hormone with multi-functional properties. Reports suggest that some of the many activities of DHEA are due to its protective effect against lipid peroxidation. Nevertheless, the antioxidant properties of DHEA are still the subject of debate. The aim was to evaluate whether its two opposed effects on lipid peroxidation reported in the literature may be dependent on schedule and doses used. Methods: Chang liver cells, a line derived from normal human liver, were grown in media containing either no steroids (control) or DHEA at concentrations ranging from 0.1 mmol/l to 50 mmol/l. At specific times, cultures were halted and cells received a pro-oxidant stimulus (cumene (CuOOH) 0.5 mmol/l), at which time cell viability (by trypan blue staining and lactate dehydrogenase (LDH) release) and thiobarbituric acid reactive substances (TBARS) concentration (spectrophotometrical assay) were evaluated. Results: At concentrations ranging from 0.1 mmol/l to 1 mmol/l, DHEA protects Chang liver cells against lipid peroxidation and/or death induced by cumene. This effect disappears if the concentration is increased to 10 mmol/l; at higher concentrations (50 mmol/l) a pro-oxidant/cytotoxic effect of DHEA appears. Conclusions: DHEA exhibits two opposed effects on lipid peroxidation; depending on its concentration it acts either to limit or to induce oxidative stress. The threshold concentration at which the pro-oxidant activity of DHEA prevails is not far in excess of that having an antioxidant effect. Either effect of DHEA on lipid peroxidation is only evident after a 'lag-phase'.

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Dehydroepiandrosterone protects bovine retinal capillary pericytes against glucose toxicity

Cited by 47 publications

References 36 publications

Low Serum Testosterone Concentration in Middle-aged Men with Type 2 Diabetes

Low Serum Testosterone Concentration in Middle-aged Men with Type 2 Diabetes

A study of capillary pericyte viability on extracellular matrix produced by endothelial cells in high glucose

Protective effect of dehydroepiandrosterone against lipid peroxidation in a human liver cell line

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