TRPV2 knockout mice demonstrate an improved cardiac performance following myocardial infarction due to attenuated activity of peri-infarct macrophages

Entin–Meer, Michal; Cohen, Lena; Hertzberg-Bigelman, Einat; Lévy, R.; Ben-Shoshan, Jeremy; Keren, Gad

doi:10.1371/journal.pone.0177132

Cited by 41 publications

(32 citation statements)

References 30 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…While several roles of TRPV2 for proper organ or cellular function have been described (11,(33)(34)(35)(36), biophysical studies on TRPV2 are scarce. The lack of selective TRPV2 agonists as well as the high heat threshold for activation hamper detailed in vitro analyses.…”

Section: Discussionmentioning

confidence: 99%

Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2

Leffler

Echtermeyer

Zielke

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Thermosensitive transient receptor potential (TRP) ion channels detect changes in ambient temperature to regulate body temperature and temperature-dependent cellular activity. Rodent orthologs of TRP vanilloid 2 (TRPV2) are activated by nonphysiological heat exceeding 50 °C, and human TRPV2 is heat-insensitive. TRPV2 is required for phagocytic activity of macrophages which are rarely exposed to excessive heat, but what activates TRPV2 in vivo remains elusive. Here we describe the molecular mechanism of an oxidation-induced temperature-dependent gating of TRPV2. While high concentrations of H2O2 induce a modest sensitization of heat-induced inward currents, the oxidant chloramine-T (ChT), ultraviolet A light, and photosensitizing agents producing reactive oxygen species (ROS) activate and sensitize TRPV2. This oxidation-induced activation also occurs in excised inside-out membrane patches, indicating a direct effect on TRPV2. The reducing agent dithiothreitol (DTT) in combination with methionine sulfoxide reductase partially reverses ChT-induced sensitization, and the substitution of the methionine (M) residues M528 and M607 to isoleucine almost abolishes oxidation-induced gating of rat TRPV2. Mass spectrometry on purified rat TRPV2 protein confirms oxidation of these residues. Finally, macrophages generate TRPV2-like heat-induced inward currents upon oxidation and exhibit reduced phagocytosis when exposed to the TRP channel inhibitor ruthenium red (RR) or to DTT. In summary, our data reveal a methionine-dependent redox sensitivity of TRPV2 which may be an important endogenous mechanism for regulation of TRPV2 activity and account for its pivotal role for phagocytosis in macrophages.

show abstract

Section: Discussionmentioning

confidence: 99%

Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2

Leffler

Echtermeyer

Zielke

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The results of previous studies have demonstrated that TRPV2 has a key role in macrophage phagocytosis, and one study revealed that TRPV2 is involved in the earliest stages of phagocytosis (37,(43)(44)(45). In addition, TRPV2 functions in intra-and extracellular Ca 2+ mobilization, and it has a role in lipopolysaccharide-induced cytokine production in macrophages (46).…”

Section: Discussionmentioning

confidence: 99%

Organ‑specific expression of the divalent ion channel proteins NCKX3, TRPV2, CTR1, ATP7A, IREG1 and HEPH in various canine organs

2018

View full text Add to dashboard Cite

Transmembrane cation channels include those for calcium, copper and iron ion transport. Each channel has physiological significance, and all have been associated with disease. However, the comparative study of transcriptional‑translational levels in canine organs has not been previously reported. In the present study, organ‑specific expression of calcium channels, including sodium/potassium/calcium exchanger 3 (NCKX3) and transient receptor potential cation channel subfamily V member 2 (TRPV2), copper channels, including high affinity copper uptake protein 1 (CTR1) and copper‑transporting ATPase 1 (ATP7A), and iron channels, including iron‑regulated transporter 1 (IREG1) and hephaestin (HEPH) proteins and their mRNAs were examined in the canine duodenum, kidney, spleen and liver. NCKX3 protein expression was highest in the kidney, moderate in the duodenum, and lowest in the spleen and liver, whereas TRPV2 protein was highly expressed in the kidney, duodenum and liver, and was low in the spleen. The CTR1 protein expression level was highest in the liver, followed (in descending order) by the duodenum, kidney and spleen. The ATP7A protein expression level was highest in the duodenum and lowest in the spleen. The IREG1 protein expression level was highest in the liver, followed (in descending order) by the kidney, duodenum and spleen. The HEPH protein level was high in liver, moderate in the duodenum and kidney, and low in the spleen. The results of the immunohistochemistry analysis demonstrated ion channel protein localizations. These results suggested that cation channel proteins are differentially expressed among canine organs, and they may be involved in organ‑specific functions associated with the maintenance of physiological homeostasis.

show abstract

“…Although TRPV2 has been shown to be located intracellularly and translocates to the sarcolemma under stress, the effect of Tranilast does not seem to be mediated through its effects on myocytes [180]. TRPV2 is also expressed in other cell types, such as macrophages, and in fact, TRPV2 knockout improves heart performance after myocardial infarction due to attenuated activity of peri-infarct macrophages [181]. TRPV2 is also highly expressed in cardiac fibroblasts and has been shown to regulate dermal fibroblast differentiation [211].…”

Section: Trpv2 and Cardiac Fibrosismentioning

confidence: 99%

Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases

Feng

Armillei

et al. 2019

JCDD

View full text Add to dashboard Cite

Cardiac fibrosis is the excessive deposition of extracellular matrix proteins by cardiac fibroblasts and myofibroblasts, and is a hallmark feature of most heart diseases, including arrhythmia, hypertrophy, and heart failure. This maladaptive process occurs in response to a variety of stimuli, including myocardial injury, inflammation, and mechanical overload. There are multiple signaling pathways and various cell types that influence the fibrogenesis cascade. Fibroblasts and myofibroblasts are central effectors. Although it is clear that Ca2+ signaling plays a vital role in this pathological process, what contributes to Ca2+ signaling in fibroblasts and myofibroblasts is still not wholly understood, chiefly because of the large and diverse number of receptors, transporters, and ion channels that influence intracellular Ca2+ signaling. Intracellular Ca2+ signals are generated by Ca2+ release from intracellular Ca2+ stores and by Ca2+ entry through a multitude of Ca2+-permeable ion channels in the plasma membrane. Over the past decade, the transient receptor potential (TRP) channels have emerged as one of the most important families of ion channels mediating Ca2+ signaling in cardiac fibroblasts. TRP channels are a superfamily of non-voltage-gated, Ca2+-permeable non-selective cation channels. Their ability to respond to various stimulating cues makes TRP channels effective sensors of the many different pathophysiological events that stimulate cardiac fibrogenesis. This review focuses on the mechanisms of Ca2+ signaling in fibroblast differentiation and fibrosis-associated heart diseases and will highlight recent advances in the understanding of the roles that TRP and other Ca2+-permeable channels play in cardiac fibrosis.

show abstract

TRPV2 knockout mice demonstrate an improved cardiac performance following myocardial infarction due to attenuated activity of peri-infarct macrophages

Cited by 41 publications

References 30 publications

Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2

Oxidation of methionine residues activates the high-threshold heat-sensitive ion channel TRPV2

Organ‑specific expression of the divalent ion channel proteins NCKX3, TRPV2, CTR1, ATP7A, IREG1 and HEPH in various canine organs

Ca2+ Signaling in Cardiac Fibroblasts and Fibrosis-Associated Heart Diseases

Contact Info

Product

Resources

About