Homocysteine &amp; its metabolite homocysteine-thiolactone &amp; deficiency of copper in patients with age related macular degeneration - A pilot study

Bharathselvi, Muthuvel; Biswas, Sayantan; Raman, Rajiv; Selvi, Radhakrishnan; Coral, Karunakaran; Narayanansamy, Angayarkanni; Ramakrishnan, Sivaramakrishnan; Sulochana, K N

doi:10.4103/0971-5916.192026

Cited by 8 publications

(7 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study showed hyperhomocysteinemia in the CFD group. Elevated homocysteine levels led to increased levels of its metabolite homocysteine thiolactone [ 42 ]. Homocysteine thiolactone could inhibit insulin receptor tyrosine kinase activity, which resulted in decreased phosphatidylinositol 3-kinase activity, and attenuate the phosphorylation of Akt [ 43 – 44 ].…”

Section: Discussionmentioning

confidence: 99%

Chronic folate deficiency induces glucose and lipid metabolism disorders and subsequent cognitive dysfunction in mice

Zhao

Yuan

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

Previous studies have shown that folate levels were decreased in patients with type 2 diabetes (T2D) and further lowered in T2D patients with cognitive impairment. However, whether folate deficiency could cause T2D and subsequent cognitive dysfunction is still unknown. The present study aimed to explore the effects of chronic folate deficiency (CFD) on glucose and lipid metabolism and cognitive function in mice. Seven-week-old mice were fed with either a CFD or control diet for 25 weeks. Serum folate was significantly reduced, whereas serum total homocysteine was significantly increased in the CFD group. Moreover, CFD induced obesity after a 6-week diet treatment, glucose intolerance and insulin resistance after a 16-week-diet treatment. In addition, CFD reduced the hepatic p-Akt/Akt ratio in response to acute insulin administration. Moreover, CFD increased serum triglyceride levels, upregulated hepatic Acc1 and Fasn mRNA expression, and downregulated hepatic Cd36 and ApoB mRNA expression. After a 24-week diet treatment, CFD induced anxiety-related activities and impairment of spatial learning and memory performance. This study demonstrates that folate deficiency could induce obesity, glucose and lipid metabolism disorders and subsequent cognitive dysfunction.

show abstract

Section: Discussionmentioning

confidence: 99%

Chronic folate deficiency induces glucose and lipid metabolism disorders and subsequent cognitive dysfunction in mice

Zhao

Yuan

et al. 2018

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…Plasma Total GSH Human AMD patients [46] Exudative AMD Plasma Total GSH Human ex-AMD patients [47] Exudative AMD on regulating GSH levels, especially mitochondrial GSH (mGSH), which could help to modulate disease risk or progression.…”

Section: Wolfram Syndrome 1 (Ws)mentioning

confidence: 99%

Glutathione Metabolism and the Novel Role of Mitochondrial GSH in Retinal Degeneration

2021

View full text Add to dashboard Cite

Glutathione (GSH) is present ubiquitously, and its role as a crucial cellular antioxidant in tissues, including the retina, is well established. GSH’s antioxidant function arises from its ability to scavenge reactive oxygen species or to serve as an essential cofactor for GSH S-transferases and peroxidases. This review summarizes the general functions, retinal distribution, disorders linked to GSH deficiency, and the emerging role for mitochondrial GSH (mGSH) in retinal function. Though synthesized only in the cytosol, the presence of GSH in multiple cell organelles suggests the requirement for its active transport across organellar membranes. The localization and distribution of 2-oxoglutarate carrier (OGC) and dicarboxylate carrier (DIC), two recently characterized mitochondrial carrier proteins in RPE and retina, show that these transporters are highly expressed in human retinal pigment epithelium (RPE) cells and retinal layers, and their expression increases with RPE polarity in cultured cells. Depletion of mGSH levels via inhibition of the two transporters resulted in reduced mitochondrial bioenergetic parameters (basal respiration, ATP production, maximal respiration, and spare respiratory capacity) and increased RPE cell death. These results begin to reveal a critical role for mGSH in maintaining RPE bioenergetics and cell health. Thus, augmentation of mGSH pool under GSH-deficient conditions may be a valuable tool in treating retinal disorders, such as age-related macular degeneration and optic neuropathies, whose pathologies have been associated with mitochondrial dysfunction.

show abstract

“…Several metabolites are associated with LDL oxidation. Elevated plasma homocysteine (Hcy) as well as homocysteine thiolactone (HCTL), are metabolites associated with the AMD pathology [12–14] as excess homocysteine affects the RPE structure and function [15]. Hcy brings about LDL oxidation through modification of LDL apoB [16].…”

Section: Introductionmentioning

confidence: 99%

Oxidized LDL, homocysteine, homocysteine thiolactone and advanced glycation end products act as pro-oxidant metabolites inducing cytokine release, macrophage infiltration and pro-angiogenic effect in ARPE-19 cells

2019

View full text Add to dashboard Cite

Age-related Macular Degeneration (AMD) is one of the major vision-threatening diseases of the eye. Oxidative stress is one of the key factors in the onset and progression of AMD. In this study, metabolites associated with AMD pathology more so at the systemic level namely, oxidized LDL (oxLDL), homocysteine (Hcy), homocysteine thiolactone (HCTL), advanced glycation end product (AGE) were evaluated for their pro-oxidant nature in a localized ocular environment based on in vitro studies in human retinal pigment epithelial cells (ARPE-19 cells). Human ARPE-19 cells were treated with pro-oxidants 50 μg/mL oxLDL, 500 μM Hcy, 500 nM HCTL, 100 μg/mL AGE, 200 μM H 2 O 2 and 200 μM H 2 O 2 with and without pre-treatment of 5 mM N-acetyl cysteine (NAC). The cytokines IL-6, IL-8 and vascular endothelial growth factor (VEGF) secreted from ARPE-19 cells exposed to pro-oxidants were estimated by ELISA. In vitro angiogenesis assay was performed with conditioned media of the pro-oxidant treated ARPE-19 cells in Geltrex-Matrigel coated 96-well plate. The human acute monocytic leukemia cell line (THP-1) was differentiated into macrophages and its migration in response to conditioned media of ARPE-19 cells insulted with the pro-oxidants was studied by transwell migration assay. Western blot was performed to detect the protein expression of Bax, Bcl-2 and NF-κB to assess apoptotic changes. The compounds involved in the study showed a significant increase in reactive oxygen species (ROS) generation in ARPE-19 cells (oxLDL; Hcy; AGE: p < 0 . 001 and HCTL: p < 0 . 05 ). NAC pre-treatment significantly lowered the oxidative stress brought about by pro-oxidants as seen by lowered ROS and MDA levels in the cells. Treatment with pro-oxidants significantly increased the secretion of IL-6 (oxLDL: p < 0 . 05 ; Hcy, HCTL and AGE: p < 0 . 01 ) and IL-8 cytokines (oxLDL: p < 0 . 05 ; HCTL: p < . 001 and AGE: p < 0 . 01 ) in ARPE-19 cells. Serum samples of AMD patients (n = 23) revealed significantly higher IL-6 and IL-8 levels compared to control subjects (n = 23) (IL6: p < 0 . 01 and IL8: p < 0 . 05 ). The pro-oxidants also promoted VEGF secretion by ARPE-19 cells compared to untreated control (oxLDL: p < 0 . 001 ; Hcy: p < 0 . 01 ; HCTL and AGE: p < 0 . 05 ). In vitro angiogenesis assay showed that the conditioned media significantly incr...

show abstract

Homocysteine & its metabolite homocysteine-thiolactone & deficiency of copper in patients with age related macular degeneration - A pilot study

Cited by 8 publications

References 28 publications

Chronic folate deficiency induces glucose and lipid metabolism disorders and subsequent cognitive dysfunction in mice

Chronic folate deficiency induces glucose and lipid metabolism disorders and subsequent cognitive dysfunction in mice

Glutathione Metabolism and the Novel Role of Mitochondrial GSH in Retinal Degeneration

Oxidized LDL, homocysteine, homocysteine thiolactone and advanced glycation end products act as pro-oxidant metabolites inducing cytokine release, macrophage infiltration and pro-angiogenic effect in ARPE-19 cells

Contact Info

Product

Resources

About