Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein

Chen, Junqin; Cha-Molstad, Hyunjoo; Szabó, Anna; Shalev, Anath

doi:10.1152/ajpendo.90944.2008

Cited by 102 publications

(99 citation statements)

References 39 publications

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“…In this study, our results showed that TXNIP expression was significantly increased in the diabetic rat hearts, at both mRNA level and protein level. This is consistent with other reports in many types of cells including cardiomyocytes [39], and even in human diabetes [40]. High glucose has been identified as an important trigger of TXNIP upregulation.…”

Section: Discussionsupporting

confidence: 93%

Variations of thioredoxin system contributes to increased susceptibility to apoptosis in cardiomyocytes of type 2 diabetic rats

Zhao¹,

Zhang²,

Li³

et al. 2014

ABBS

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Cardiac complications are the leading cause of death in diabetes. However, the mechanism of diabetes in inducing myocardial injury and apoptosis, and whether the thioredoxin (Trx) system is involved remain unclear. In this study, male Sprague -Dawley rats were randomly divided into two groups: the control and the diabetes groups, and then were randomly divided into five different timepoints (the 1st, 2nd, 4th, 12th, and 24th week). The results showed that diabetes-induced cardiac injury was enhanced in the type 2 diabetes rats, as evidenced by aggravated cardiac dysfunction, biochemical indicators, and increased myocardial apoptosis (TUNEL and caspase-3 activity). The activity of myocardial Trx and Trx reductase (TR) in diabetic rats was significantly decreased from the second week and continually aggravated with the disease progression. In diabetic rats, the mRNA expression of Trx1, Trx2, TR1, and TR2 was decreased first and then increased after the fourth week. Meanwhile, the protein expression of these Trx system members was significantly increased at the 12th week. Trx nitration was cleared, the Trx/ASK1 interaction was significantly decreased, and the activity of p38 was significantly enhanced in cardiac tissues at the 12th week. These results demonstrated that diabetes may cause myocardial injury and apoptosis, and the extent of which was accompanied with the development of the disease. The mechanism is associated with the development of diabetes and the decreased activity of Trx and TR. The reasons for decreased Trx activity may include: decrease of Trx and TR protein expression; nitration modification of Trx; and up-regulation of TXNIP expression.

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Section: Discussionsupporting

confidence: 93%

Variations of thioredoxin system contributes to increased susceptibility to apoptosis in cardiomyocytes of type 2 diabetic rats

Zhao¹,

Zhang²,

Li³

et al. 2014

ABBS

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“…A recent study demonstrated that inhibiting TXNIP using calcium channel blockers can prevent cardiac apoptosis. 31 This is of importance as reduced Trx has also been shown to play a key role in regulating apoptosis pathway by binding to ASK-1 through redox active site of Trx. 32 Thus, inactivation of Trx through oxidation or interaction with TXNIP leads to release and activation of the apoptotic ASK-1.…”

Section: Figure 5 Fetpps Blocked Activation Of P38 Mapk Apoptosis Pamentioning

confidence: 99%

Neurovascular Protective Effect of FeTPPs in N-Methyl-D-Aspartate Model

Al‐Gayyar

Abdelsaid

Matragoon

et al. 2010

The American Journal of Pathology

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We have previously shown a causal role of peroxynitrite in mediating retinal ganglion cell (RGC) death in diabetic and neurotoxicity models. In the present study, the role of peroxynitrite in altering the antioxidant and antiapoptotic thioredoxin (Trx) system will be investigated as well as the subsequent effects on glial activation and capillary degeneration. Excitotoxicity of the retina was induced by intravitreal injection of N-methyl-Daspartate (NMDA) in rats, which also received the peroxynitrite decomposition catalyst FeTPPs. Retinal ganglion cell (RGC) death plays a critical role in the pathogenesis of many retinal neurodegenerative disorders, including glaucoma, diabetic retinopathy, traumatic optic neuropathy, uveitis, and retinal ischemia. [1][2][3][4][5] Understanding the molecular mechanism of neuronal cell death in such retinal diseases is of great clinical important for devising new treatments. In response to traumatic or ischemic injury, excessive activation of glutamate receptors has been implicated in the RGC death process. 6 Therefore, administration of N-methyl-D-aspartate (NMDA) to rodent eyes is a reliable model to study RGC death. Excessive NMDA receptor stimulation leads to excessive Ca 2ϩ influx, 7 which in turn triggers formation of nitric oxide 8 and accumulation of superoxides and their combination product peroxynitrite, causing lipid peroxidation, DNA damage and the eventual cell death. 9 Although increases in reactive oxygen species (ROS) and peroxynitrite have been implicated in mediating RGC death, 1,6 the molecular mechanisms by which peroxynitrite causes RGC death are not fully elucidated.Protection from ROS is mediated by superoxide dismutase, glutathione, and thioredoxin (Trx) systems. 10,11

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“…Throughout the process of apoptosis, proteins of the caspase and Bcl-2 families have crucial roles. Apoptosis is an important mechanism of myocardial cell damage in diabetic disease, and proteins of the caspase and Bcl-2 families are also involved (Li et al, 2008;Chen et al, 2009;Liu et al, 2009;Thandavarayan et al, 2009). CASP3 is a member of the caspase family and has been recognized as an important initiator and promoter of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Cardiac apoptosis as a major early cellular response in DM is induced by hyperglycemia-derived oxidative stress that activates a mitochondrial cytochrome c-mediated CASP3 pathway (Cai et al, 2006). Cleaved CASP3 has also been found to be elevated in vivo in STZ-and obesity-induced DM mice (Li et al, 2008;Chen et al, 2009). Down-regulation of CASP3 can prevent diabetes-and angiotensin II-induced cardiac endoplasmic reticular stress and associated cell death (Xu et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats

Zhen

Pang

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:We evaluated the cardioprotective effects of ginsenoside Rg1 in a diabetic rat model induced with high-fat diet and intraperitoneal injection of streptozotocin. Ginsenoside Rg1 was injected intraperitoneally for 12 weeks. Myocardial injury indices and oxidative stress markers were determined. Changes in cardiac ultrastructure were evaluated with transmission electron microscopy. Myocardial apoptosis was assessed via terminal deoxynucleotidyl transferase (TDT)-mediated DNA nick-end labeling (TUNEL) and immunohistochemistry. Ginsenoside Rg1 was associated with a significant dose-dependent reduction in serum levels of creatinine kinase MB and cardiac troponin I, and lessened ultrastructural disorders in diabetic myocardium, relative to the untreated diabetic model rats. Also, compared with the untreated diabetic rats, significant reductions in serum and myocardial levels of malondialdehyde were noted in the ginsenoside Rg1-treated groups, and increased levels of the antioxidants (superoxide dismutase, catalase, and glutathione peroxidase) were detected. TUNEL staining indicated reduced myocardial apoptosis in ginsenoside Rg1-treated rats, which may be associated with reduced levels of caspase-3 (CASP3) and increased levels of B-cell lymphoma-extra-large (Bcl-xL) in the diabetic myocardium. Ginsenoside Rg1 treatment of diabetic rats was associated with reduced oxidative stress and attenuated myocardial apoptosis, suggesting that ginsenoside Rg1 may be of potential preventative and therapeutic value for cardiovascular injury in diabetic patients.

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Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein

Abstract: Chen J, Cha-Molstad H, Szabo A, Shalev A. Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein.

Cited by 102 publications

References 39 publications

Variations of thioredoxin system contributes to increased susceptibility to apoptosis in cardiomyocytes of type 2 diabetic rats

Variations of thioredoxin system contributes to increased susceptibility to apoptosis in cardiomyocytes of type 2 diabetic rats

Neurovascular Protective Effect of FeTPPs in N-Methyl-D-Aspartate Model

Ginsenoside Rg1 ameliorates oxidative stress and myocardial apoptosis in streptozotocin-induced diabetic rats

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