Tag: TRPM7

Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multisystemic disorder responsible for significant disability. Although a unifying etiology for ME/CFS is uncertain, impaired natural killer (NK) cell cytotoxicity represents a consistent and measurable feature of this disorder.

Research utilizing patient-derived NK cells has implicated dysregulated calcium (Ca2+) signaling, dysfunction of the phosphatidylinositol-4,5-bisphosphate (PIP2)-dependent cation channel, transient receptor potential melastatin (TRPM) 3, as well as altered surface expression patterns of TRPM3 and TRPM2 in the pathophysiology of ME/CFS. TRPM7 is a related channel that is modulated by PIP2 and participates in Ca2+ signaling. Though TRPM7 is expressed on NK cells, the role of TRPM7 with IL-2 and intracellular signaling mechanisms in the NK cells of ME/CFS patients is unknown.

This study examined the effect of IL-2 stimulation and TRPM7 pharmacomodulation on NK cell cytotoxicity using flow cytometric assays as well as co-localization of TRPM7 with PIP2 and cortical actin using confocal microscopy in 17 ME/CFS patients and 17 age- and sex-matched healthy controls. The outcomes of this investigation are preliminary and indicate that crosstalk between IL-2 and TRMP7 exists. A larger sample size to confirm these findings and characterization of TRPM7 in ME/CFS using other experimental modalities are warranted.

Source: Du Preez S, Eaton-Fitch N, Cabanas H, Staines D, Marshall-Gradisnik S. Characterization of IL-2 Stimulation and TRPM7 Pharmacomodulation in NK Cell Cytotoxicity and Channel Co-Localization with PIP2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Int J Environ Res Public Health. 2021 Nov 12;18(22):11879. doi: 10.3390/ijerph182211879. PMID: 34831634. https://pubmed.ncbi.nlm.nih.gov/34831634/

Potential Implications of Mammalian Transient Receptor Potential Melastatin 7 in the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review

Abstract:

The transient receptor potential (TRP) superfamily of ion channels is involved in the molecular mechanisms that mediate neuroimmune interactions and activities. Recent advancements in neuroimmunology have identified a role for TRP cation channels in several neuroimmune disorders including amyotropic lateral sclerosis, multiple sclerosis, and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). ME/CFS is a debilitating disorder with an obscure aetiology, hence considerable examination of its pathobiology is warranted. Dysregulation of TRP melastatin (TRPM) subfamily members and calcium signalling processes are implicated in the neurological, immunological, cardiovascular, and metabolic impairments inherent in ME/CFS.

In this review, we present TRPM7 as a potential candidate in the pathomechanism of ME/CFS, as TRPM7 is increasingly recognized as a key mediator of physiological and pathophysiological mechanisms affecting neurological, immunological, cardiovascular, and metabolic processes. A focused examination of the biochemistry of TRPM7, the role of this protein in the aforementioned systems, and the potential of TRPM7 as a molecular mechanism in the pathophysiology of ME/CFS will be discussed in this review. TRPM7 is a compelling candidate to examine in the pathobiology of ME/CFS as TRPM7 fulfils several key roles in multiple organ systems, and there is a paucity of literature reporting on its role in ME/CFS.

Source: Du Preez S, Cabanas H, Staines D, Marshall-Gradisnik S. Potential Implications of Mammalian Transient Receptor Potential Melastatin 7 in the Pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Review. Int J Environ Res Public Health. 2021 Oct 12;18(20):10708. doi: 10.3390/ijerph182010708. PMID: 34682454; PMCID: PMC8535478. https://pubmed.ncbi.nlm.nih.gov/34682454/ (Full text)