Differential regulation of TRPV1 channels by H2O2: implications for diabetic microvascular dysfunction

DelloStritto, Daniel J.; Connell, Patrick J.; Dick, Gregory M.; Fancher, Ibra S.; Klarich, Brittany; Fahmy, Joseph N.; Kang, Patrick T.; Chen, Yeong Renn; Damron, Derek S.; Thodeti, Charles K.; Bratz, Ian N.

doi:10.1007/s00395-016-0539-4

Cited by 38 publications

(42 citation statements)

References 66 publications

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“…Mechanical hypersensitivity induced by H 2 O 2 was not sensitive to E06 blockade. H 2 O 2 is a highly reactive radical that activates not only TRPA1 and TRPV1 channels (Keeble et al ., ) but also TRPM2 and TRPC5 channels (Andersson et al ., ; Naylor et al ., ; DelloStritto et al ., ).…”

Section: Discussionmentioning

confidence: 97%

Antinociception by the anti‐oxidized phospholipid antibody E06

Mohammadi

Oehler

Kloka

et al. 2018

British J Pharmacology

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These authors contributed equally. BACKGROUND AND PURPOSEROS and their downstream molecules such as oxidized phospholipids (OxPL) and 4-hydroxynonenal activate TRPA1 and TRPV1 (vanilloid 1) cation channels in vivo and in vitro shaping thermal and mechanical hypersensitivity in inflammatory pain. E06/T15 is a monoclonal autoantibody against oxidized phosphatidylcholine (OxPC) used in diagnostics in arteriosclerosis. Recently, we provided evidence that E06 also ameliorates inflammatory pain. Here, we studied E06 for local treatment against hypersensitivity evoked by endogenous and exogenous agonists of TRPA1 or TRPV1 channels. EXPERIMENTAL APPROACHWe utilized a combination of reflexive and complex behavioural pain measurements, live-cell calcium imaging and OxPC-binding assays. The lipid peroxidation metabolite 4-hydroxynonenal, hydrogen peroxide as a source of ROS, allyl isothiocyanate and capsaicin were used to activate their respective receptors. KEY RESULTSAll irritants induced thermal and mechanical hypersensitivity, spontaneous nocifensive and affective-motivational behaviour, as well as calcium influx in HEK TRPA1 -or HEK TRPV1 -cells and dorsal root ganglion neurons. E06 prevented prolonged mechanical hypersensitivity induced by all irritants except for H 2 O 2 . E06 did not alter immediate irritant-induced nocifensive or affective motivational behaviour. In vitro, E06 blocked only 4-hydroxynonenal-induced calcium influx although this compound did not bind to E06. After 1-3 h, all tested irritants elicited formation of OxPC in paw tissue. CONCLUSIONS AND IMPLICATIONSE06 ameliorates not only inflammatory pain but also prolonged hypersensitivity due to formation of OxPC. This supports the view that neutralizing certain OxPL as endogenous activators of TRPA1 or TRPV1 channels may be valuable for pain therapy. Abbreviations

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Section: Discussionmentioning

confidence: 97%

Antinociception by the anti‐oxidized phospholipid antibody E06

Mohammadi

Oehler

Kloka

et al. 2018

British J Pharmacology

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“…; DelloStritto et al . ) expressed by vascular cells. Ageing decreases L‐type channel expression and associated membrane currents in mesenteric arteries and aorta (Fukuda et al .…”

Section: Discussionmentioning

confidence: 99%

Advanced age protects resistance arteries of mouse skeletal muscle from oxidative stress through attenuating apoptosis induced by hydrogen peroxide

Norton

Sinkler

Jacobsen

et al. 2019

The Journal of Physiology

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Key pointsr Vascular oxidative stress increases with advancing age. r We hypothesized that resistance vessels develop resilience to oxidative stress to protect functional integrity and tested this hypothesis by exposing isolated pressurized superior epigastric arteries (SEAs) of old and young mice to H 2 O 2 . r H 2 O 2 -induced death was greater in smooth muscle cells (SMCs) than endothelial cells (ECs) and lower in SEAs from old vs. young mice; the rise in vessel wall [Ca 2+ ] i induced by H 2 O 2 was attenuated with ageing, as was the decline in noradrenergic vasoconstriction; genetic deletion of IL-10 mimicked the effects of advanced age on cell survival. r Inhibiting NO synthase or scavenging peroxynitrite reduced SMC death; endothelial denudation or inhibiting gap junctions increased SMC death; delocalization of cytochrome C activated caspases 9 and 3 to induce apoptosis.r Vascular cells develop resilience to H 2 O 2 during ageing by preventing Ca 2+ overload and endothelial integrity promotes SMC survival.Abstract Advanced age is associated with elevated oxidative stress and can protect the endothelium from cell death induced by H 2 O 2 . Whether such protection occurs for intact vessels or differs between smooth muscle cell (SMC) and endothelial cell (EC) layers is unknown. We tested the hypothesis that ageing protects SMCs and ECs during acute exposure to H 2 O 2 (200 µM, 50 min). Mouse superior epigastric arteries (SEAs; diameter, ß150 µm) were isolated and pressurized to 100 cmH 2 O at 37˚C. For SEAs from young (4 months) mice, H 2 O 2 killed 57% of SMCs and 11% of ECs in males vs. 8% and 2%, respectively, in females. Therefore, SEAs from males were studied to resolve the effect of ageing and experimental interventions. For old (24 months) Charles E. Norton III is currently a postdoctoral fellow in Steven Segal's laboratory at the University of Missouri, Columbia. His interest in vascular physiology developed as an undergraduate and PhD student studying mechanisms of chronic hypoxia-induced pulmonary hypertension at the University of New Mexico. Dr Norton's primary interest is in understanding how chemical and electrical communication between endothelial cells and smooth muscle cells modulate vasomotor tone and cell death. Currently, he is exploring how conditions of chronic oxidative stress alter resilience to apoptosis.C. E. Norton and others J Physiol 597.15 mice, SMC death was reduced to 10% with diminished accumulation of [Ca 2+ ] i in the vessel wall during H 2 O 2 exposure. In young mice, genetic deletion of IL-10 mimicked the protective effect of ageing on cell death and [Ca 2+ ] i accumulation. Whereas endothelial denudation or gap junction inhibition (carbenoxolone; 100 µM) increased SMC death, inhibiting NO synthase (L-NAME, 100 µM) or scavenging peroxynitrite (FeTPPS, 5 µM) reduced SMC death along with [Ca 2+ ] i . Despite NO toxicity via peroxynitrite formation, endothelial integrity protects SMCs. Caspase inhibition (Z-VAD-FMK, 50 µM) attenuated cell death with immunostaining for annex...

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“…Noteworthy, pathologically prolonged H 2 O 2 exposure disrupts TRPV1‐dependent coronary vascular signalling, which may result in reduced tissue perfusion characteristic for diabetes (DelloStritto et al . ). In diabetes, mesenteric arteries also show reduced functional expression of TRPV1, which contributes to impaired relaxation.…”

Section: Transient Receptor Potential Channelsmentioning

confidence: 97%

Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2

et al. 2016

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Members of the transient receptor potential (TRP) cation channel receptor family have unique sites of regulatory function in the kidney which enables them to promote regional vasodilatation and controlled Ca influx into podocytes and tubular cells. Activated TRP vanilloid 1 receptor channels (TRPV1) have been found to elicit renoprotection in rodent models of acute kidney injury following ischaemia/reperfusion. Transient receptor potential cation channel, subfamily C, member 6 (TRPC6) in podocytes is involved in chronic proteinuric kidney disease, particularly in focal segmental glomerulosclerosis (FSGS). TRP vanilloid 4 receptor channels (TRPV4) are highly expressed in the kidney, where they induce Ca influx into endothelial and tubular cells. TRP melastatin (TRPM2) non-selective cation channels are expressed in the cytoplasm and intracellular organelles, where their inhibition ameliorates ischaemic renal pathology. Although some of their basic properties have been recently identified, the renovascular role of TRPV1, TRPV4, TRPC6 and TRPM2 channels in disease states such as obesity, hypertension and diabetes is largely unknown. In this review, we discuss recent evidence for TRPV1, TRPV4, TRPC6 and TRPM2 serving as potential targets for acute and chronic renoprotection in chronic vascular and metabolic disease.

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Differential regulation of TRPV1 channels by H2O2: implications for diabetic microvascular dysfunction

Cited by 38 publications

References 66 publications

Antinociception by the anti‐oxidized phospholipid antibody E06

Antinociception by the anti‐oxidized phospholipid antibody E06

Advanced age protects resistance arteries of mouse skeletal muscle from oxidative stress through attenuating apoptosis induced by hydrogen peroxide

Renoprotection: focus on TRPV1, TRPV4, TRPC6 and TRPM2

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