Ryuji Inoue

Dynamic remodeling of TRPC5 channel–caveolin-1–eNOS protein assembly potentiates the positive feedback interaction between Ca2+ and NO signals

Reiko Sakaguchi, Nobuaki Takahashi, Takashi Yoshida, Nozomi Ogawa et autres

The cell signaling molecules nitric oxide (NO) and Ca 2+ regulate diverse biological processes through their closely coordinated activities directed by signaling protein complexes. However, it remains unclear how dynamically the multicomponent protein assemblies behave within the signaling complexes upon the interplay …

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The Role of TRPM4 in Cardiac Electrophysiology and Arrhythmogenesis

Yaopeng Hu, Jiehui Cang, Keizo Hiraishi, Takayuki Fujita et autres

The transient receptor potential melastatin 4 (TRPM4) channel is a non-selective cation channel that activates in response to increased intracellular Ca2+ levels but does not allow Ca2+ to pass through directly. It plays a crucial role in regulating diverse cellular functions associated …

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Critical contributions of pre-S1 shoulder and distal TRP box in DAG-activated TRPC6 channel by PIP2 regulation

Masayuki X Mori, Ryo Okada, Reiko Sakaguchi, Hideharu Hase et autres

Abstract Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2 or PIP2) regulates the activities of numerous membrane proteins, including diacylglycerol(DAG)-activated TRPC3/6/7 channels. Although PIP2 binding is known to support DAG-activated TRP channel activity, its binding site remains unknown. We screened for PIP2 binding sites within TRPC6 channels …

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Potential of the TRPM7 channel as a novel therapeutic target for pulmonary arterial hypertension

Keizo Hiraishi, Lin Hai Kurahara, Kaori Ishikawa, Tetsuhiko Go et autres

Pulmonary arterial hypertension (PAH) is an intractable vascular disease characterized by a progressive increase in pulmonary vascular resistance caused by pulmonary vascular remodeling, which ultimately leads to right-sided heart failure. PAH remains incurable, despite the development of PAH-targeted therapeutics centered on pulmonary …

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Theoretical Investigation of the Mechanism by which A Gain-of-Function Mutation of the TRPM4 Channel Causes Conduction Block

Yaopeng Hu, Qin Li, Yanghua Shen, Takayuki Fujita et autres

In the heart, TRPM4 is most abundantly distributed in the conduction system. Previously, a single mutation, ‘E7K’, was identified in its distal N-terminus to cause conduction disorder because of enhanced cell-surface expression. It remains, however, unclear how this expression increase leads to …

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An Arrhythmic Mutation E7K Facilitates TRPM4 Channel Activation via Enhanced PIP2 Interaction

Yaopeng Hu, Qin Li, Lin-Hai Kurahara, Narumi Shioi et autres

A Ca2+-activated monovalent cation-selective TRPM4 channel is abundantly expressed in the heart. Recently, a single gain-of-function mutation identified in the distal N-terminus of the human TRPM4 channel (Glu5 to Lys5; E7K) was found to be arrhythmogenic because of enhanced cell membrane expression. …

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Substantial involvement of TRPM7 inhibition in the therapeutic effect of Ophiocordyceps sinensis on pulmonary hypertension

Keizo Hiraishi, Lin Hai Kurahara, Jianlin Feng, Aya Yamamura et autres

Ophiocordyceps sinensis (OCS), an entomopathogenic fungus, is known to exert antiproliferative and antitissue remodeling effects. Vascular remodeling and vasoconstriction play critical roles in the development of pulmonary hypertension (PH). The therapeutic potential of OCS for PH was investigated using rodent PH models, …

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Volume-regulated chloride channel regulates cell proliferation and is involved in the possible interaction between TMEM16A and LRRC8A in human metastatic oral squamous cell carcinoma cells

Shohei Yoshimoto, Miho Matsuda, Kenichi Kato, Eijiro Jimi et autres

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Pathological activation of CaMKII induces arrhythmogenicity through TRPM4 overactivation

Yaopeng Hu, Daniela Ross‐Kaschitza, Maria C. Essers, Prakash Arullampalam et autres

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Eicosapentaenoic acid ameliorates pulmonary hypertension via inhibition of tyrosine kinase Fyn

Lin Hai Kurahara, Keizo Hiraishi, Aya Yamamura, Ying Zhang et autres

Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by pulmonary arterial vasoconstriction and remodeling. Src family tyrosine kinases, including Fyn, play critical roles in vascular remodeling via the inhibition of STAT3 signaling. EPA is known to inhibit Fyn kinase activity. This …

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Pathophysiological Contribution of TRPM7 Channel to Pulmonary Arterial Hypertension

Keizo Hiraishi, Lin-Hai Kurahara, Yuanyuan Cui, Ryuji Inoue

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SGLT2 inhibitor ipragliflozin attenuates breast cancer cell proliferation

Shiho Komatsu, Takashi Nomiyama, Tomohiro Numata, Takako Kawanami et autres

Cancer is currently one of the major causes of death in patients with type 2 diabetes mellitus. We previously reported the beneficial effects of the glucagon-like peptide-1 receptor agonist exendin-4 against prostate and breast cancer. In the present study, we examined the …

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