Nitric oxide activates PI3-K and MAPK signalling pathways in human and rat vascular smooth muscle cells: Influence of insulin resistance and oxidative stress

Doronzo, Gabriella; Viretto, Michela; Russo, Isabella; Mattiello, Luigi; Martino, Leonardo Di; Cavalot, Franco; Anfossi, Giovanni; Trovati, Mariella

doi:10.1016/j.atherosclerosis.2011.01.019

Cited by 45 publications

(35 citation statements)

References 30 publications

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“…For instance, oxidative stress can counteract the protective effects of NO through either increased NO scavenging or impairment of the NO-cGMP pathway. 53-55 As an example from our study, we found that in N-iCMs and Dys2-iCMs nicorandil decreased ROS through an NO-cGMP-dependent manner but in an NO-cGMP-independent manner in Dys1-iCMs. The increased ROS levels observed at baseline in the Dys1-iCMs may negate NO signaling.…”

Section: Discussionsupporting

confidence: 64%

Nicorandil, a Nitric Oxide Donor and ATP-Sensitive Potassium Channel Opener, Protects Against Dystrophin-Deficient Cardiomyopathy

Afzal

Reiter

Gastonguay

et al. 2016

J Cardiovasc Pharmacol Ther

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Section: Discussionsupporting

confidence: 64%

Nicorandil, a Nitric Oxide Donor and ATP-Sensitive Potassium Channel Opener, Protects Against Dystrophin-Deficient Cardiomyopathy

Afzal

Reiter

Gastonguay

et al. 2016

J Cardiovasc Pharmacol Ther

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“…Although inhibition of mTOR/p70S6K or PI 3-kinase may lead to ERK inhibition [41] or ERK activation [26–28] in different cell types, studies with adiponectin demonstrate its inhibitory effects on PDGF-induced ERK phosphorylation in human VSMCs [17]. In addition, adiponectin attenuates IGF1-induced ERK phosphorylation in rat aortic VSMCs [34].…”

Section: Discussionmentioning

confidence: 99%

AdipoRon, an adiponectin receptor agonist, attenuates PDGF-induced VSMC proliferation through inhibition of mTOR signaling independent of AMPK: Implications toward suppression of neointimal hyperplasia

Fairaq

Shawky

Osman

et al. 2017

Pharmacological Research

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Hypoadiponectinemia is associated with an increased risk of coronary artery disease. Although adiponectin replenishment mitigates neointimal hyperplasia and atherosclerosis in mouse models, adiponectin therapy has been hampered in a clinical setting due its large molecular size. Recent studies demonstrate that AdipoRon (a small-molecule adiponectin receptor agonist) improves glycemic control in type 2 diabetic mice and attenuates postischemic cardiac injury in adiponectin-deficient mice, in part, through activation of AMP-activated protein kinase (AMPK). To date, it remains unknown as to whether AdipoRon regulates vascular smooth muscle cell (VSMC) proliferation, which plays a major role in neointima formation. In the present study, oral administration of AdipoRon (50 mg/Kg) in C57BL/6J mice significantly diminished arterial injury-induced neointima formation by ~57%. Under in vitro conditions, AdipoRon treatment led to significant inhibition of platelet-derived growth factor (PDGF)-induced VSMC proliferation, DNA synthesis, and cyclin D1 expression. While AdipoRon induced a rapid and sustained activation of AMPK, it also diminished basal and PDGF-induced phosphorylation of mTOR and its downstream targets, including p70S6K/S6 and 4E-BP1. However, siRNA-mediated AMPK downregulation showed persistent inhibition of p70S6K/S6 and 4E-BP1 phosphorylation, indicating AMPK-independent effects for AdipoRon inhibition of mTOR signaling. In addition, AdipoRon treatment resulted in a sustained and transient decrease in PDGF-induced phosphorylation of Akt and ERK, respectively. Furthermore, PDGF receptor-β tyrosine phosphorylation, which controls the phosphorylation state of Akt and ERK, was diminished upon AdipoRon treatment. Together, the present findings suggest that orally-administered AdipoRon has the potential to limit restenosis after angioplasty by targeting mTOR signaling independent of AMPK activation.

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“…We then asked whether the induction of CNTF and GFAP genes was linked in GSNOtreated astrocytes. Importantly, NO/sGC/PKG signaling has been documented to activate MAPK in different cell types (44,45). Therefore, we first determined the activation status of MAPKs in GSNO-treated astrocytes.…”

Section: Gsno-mediated Induction Of Cntf Gene Is Regulated By Creb/ppmentioning

confidence: 99%

S-Nitrosoglutathione Induces Ciliary Neurotrophic Factor Expression in Astrocytes, Which Has Implications to Protect the Central Nervous System under Pathological Conditions

Paintlia

Singh

et al. 2013

Journal of Biological Chemistry

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Background: CNTF plays an important role in brain development and injury. Results: S-Nitrosoglutathione induces CNTF expression in astrocytes via NO signaling dependent PPAR-␥ transactivation. Conclusion: NO signaling in astrocytes favors the beneficial outcomes of reactive astrogliosis. Significance: Endogenously produced NO or its exogenous source has potential to modulate the outcomes of reactive astrogliosis in vivo.

show abstract

Nitric oxide activates PI3-K and MAPK signalling pathways in human and rat vascular smooth muscle cells: Influence of insulin resistance and oxidative stress

Cited by 45 publications

References 30 publications

Nicorandil, a Nitric Oxide Donor and ATP-Sensitive Potassium Channel Opener, Protects Against Dystrophin-Deficient Cardiomyopathy

Nicorandil, a Nitric Oxide Donor and ATP-Sensitive Potassium Channel Opener, Protects Against Dystrophin-Deficient Cardiomyopathy

AdipoRon, an adiponectin receptor agonist, attenuates PDGF-induced VSMC proliferation through inhibition of mTOR signaling independent of AMPK: Implications toward suppression of neointimal hyperplasia

S-Nitrosoglutathione Induces Ciliary Neurotrophic Factor Expression in Astrocytes, Which Has Implications to Protect the Central Nervous System under Pathological Conditions

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