DJ‑1 alleviates high glucose‑induced endothelial cells injury via PI3K/Akt‑eNOS signaling pathway

Tian, Hongan; Li, Shunzhen; Yu, Kai

doi:10.3892/mmr.2017.7975

Cited by 7 publications

(7 citation statements)

References 47 publications

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“…BAX localizes largely in the cytoplasm, redistributes to the mitochondria in response to stimuli, triggers the release of cytochrome c, and consequently induces mitochondrial dysfunction (55). It has been reported that LY294002 treatment inhibits the PI3K/Akt pathway, suppresses BAX translocation to the mitochondria and reduces the release of mitochondrial ROS (56). The knockdown of DHODH has been shown to increase BAX expression (57).…”

Section: Discussionmentioning

confidence: 99%

LY294002 alleviates bone cancer pain by reducing mitochondrial dysfunction and the inflammatory response

et al. 2023

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Bone cancer pain (BCP) is mainly caused by bone metastasis and markedly impairs the functional capacity and daily functions of patients. Neuroinflammation plays a pivotal role in the pathogenesis and maintenance of chronic pain. Oxidative stress in the mitochondria is a key contributor to neuroinflammation and neuropathic pain. Herein, a rat model of BCP was established which was characterized by bone destruction, pain hypersensitivity and motor disability. In the spinal cord, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling was activated, and the inflammatory response and mitochondrial dysfunction were also observed. The intrathecal injection of LY294002, a selective inhibitor of PI3K/Akt signaling, decreased mechanical pain sensitivity, suppressed spontaneous pain and recovered the motor coordination of rats with BCP. Second, LY294002 treatment blocked spinal inflammation by reducing astrocytic activation and downregulating the expression levels of inflammatory factors, such as NF-κB, IL-1β and TNF-α. Moreover, LY294002 treatment recovered mitochondrial function by activating the manganese superoxide dismutase enzyme, increasing NADH:ubiquinone oxidoreductase subunit B11 expression, and decreasing BAX and dihydroorotate dehydrogenase expression. LY294002 treatment also increased the mitochondrial membrane potential and decreased the mitochondrial reactive oxygen species levels in C6 cells. On the whole, the results of the present study suggest that the inhibition of PI3K/Akt signaling by LY294002 restores mitochondrial function, suppresses spinal inflammation and alleviates BCP.

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Section: Discussionmentioning

confidence: 99%

LY294002 alleviates bone cancer pain by reducing mitochondrial dysfunction and the inflammatory response

et al. 2023

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“…The major finding of our studies is that nitrosative stress is a novel mechanism of poor coronary collateral circulation in patients following acute MI. Current treatments of acute MI have focused on increasing NO bioavailability to induce coronary arterial relaxation (Munzel and Gori, 2013 ; Tian et al, 2018 ). However, continuous exposure to nitrate esters can lead to nitrate tolerance, causing the loss of vascular responsiveness to nitrates (Bai et al, 2018 ; Zhou et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

S-nitrosylation of AMPKγ impairs coronary collateral circulation and disrupts VSMC reprogramming

Bai,

Guo,

Wang

et al. 2023

EMBO Rep

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Collateral circulation is essential for blood resupply to the ischemic heart, which is dictated by the contractile phenotypic restoration of vascular smooth muscle cells (VSMC). Here we investigate whether S-nitrosylation of AMP-activated protein kinase (AMPK), a key regulator of the VSMC phenotype, impairs collateral circulation. In rats with collateral growth and development, nitroglycerin decreases coronary collateral blood flow (CCBF), inhibits vascular contractile phenotypic restoration, and increases myocardial infarct size, accompanied by reduced AMPK activity in the collateral zone. Nitric oxide (NO) S-nitrosylates human recombinant AMPKγ1 at cysteine 131 and decreases AMP sensitivity of AMPK. In VSMCs, exogenous expression of S-nitrosylation-resistant AMPKγ1 or deficient NO synthase (iNOS) prevents the disruption of VSMC reprogramming. Finally, hyperhomocysteinemia or hyperglycemia increases AMPKγ1 S-nitrosylation, prevents vascular contractile phenotypic restoration, reduces CCBF, and increases the infarct size of the heart in Apoe-/- mice, all of which is rescued in Apoe-/-/iNOSsm-/- mice or Apoe-/- mice with enforced expression of the AMPKγ1-C130A mutant following RI/MI. We conclude that nitrosative stress disrupts coronary collateral circulation during hyperhomocysteinemia or hyperglycemia through AMPK S-nitrosylation.

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“…Oxidative stress is a molecular disorder of reactive oxygen metabolism and plays a key role in the pathogenesis of endothelial dysfunction and atherosclerosis [ 45 , 46 ]. NADPH oxidase catalyzes the generation of ROS.…”

Section: Discussionmentioning

confidence: 99%

Citronellal Attenuates Oxidative Stress–Induced Mitochondrial Damage through TRPM2/NHE1 Pathway and Effectively Inhibits Endothelial Dysfunction in Type 2 Diabetes Mellitus

et al. 2022

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In type 2 diabetes mellitus (T2DM), oxidative stress induces endothelial dysfunction (ED), which is closely related to the formation of atherosclerosis. However, there are few effective drugs to prevent and cure it. Citronellal (CT) is an aromatic active substance extracted from citronella plants. Recently, CT has been shown to prevent ED, but the underlying mechanism remains unclear. The purpose of this study was to investigate whether CT ameliorated T2DM-induced ED by inhibiting the TRPM2/NHE1 signal pathway. Transient receptor potential channel M2 (TRPM2) is a Ca2+-permeable cation channel activated by oxidative stress, which damages endothelial cell barrier function and further leads to ED or atherosclerosis in T2DM. The Na+/H+ exchanger 1 (NHE1), a transmembrane protein, also plays an important role in ED. Whether TRPM2 and NHE1 are involved in the mechanism of CT improving ED in T2DM still needs further study. Through the evaluations of ophthalmoscope, HE and Oil red staining, vascular function, oxidative stress level, and mitochondrial membrane potential evaluation, we observed that CT not only reduced the formation of lipid deposition but also inhibited ED and suppressed oxidative stress-induced mitochondrial damage in vasculature of T2DM rats. The expressions of NHE1 and TRPM2 was up-regulated in the carotid vessels of T2DM rats; NHE1 expression was also upregulated in endothelial cells with overexpression of TRPM2, but CT reversed the up-regulation of NHE1 in vivo and in vitro. In contrast, CT had no inhibitory effect on the expression of NHE1 in TRPM2 knockout mice. Our study show that CT suppressed the expression of NHE1 and TPRM2, alleviated oxidative stress-induced mitochondrial damage, and imposed a protective effect on ED in T2DM rats.

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DJ‑1 alleviates high glucose‑induced endothelial cells injury via PI3K/Akt‑eNOS signaling pathway

Cited by 7 publications

References 47 publications

LY294002 alleviates bone cancer pain by reducing mitochondrial dysfunction and the inflammatory response

LY294002 alleviates bone cancer pain by reducing mitochondrial dysfunction and the inflammatory response

S-nitrosylation of AMPKγ impairs coronary collateral circulation and disrupts VSMC reprogramming

Citronellal Attenuates Oxidative Stress–Induced Mitochondrial Damage through TRPM2/NHE1 Pathway and Effectively Inhibits Endothelial Dysfunction in Type 2 Diabetes Mellitus

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