Last update 19 Sep 2024

CAMK2G

Last update 19 Sep 2024

Basic Info

Synonyms

calcium/calmodulin dependent protein kinase II gamma, calcium/calmodulin-dependent protein kinase (CaM kinase) II gamma, Calcium/calmodulin-dependent protein kinase type II subunit gamma

+ [6]

Introduction

Calcium/calmodulin-dependent protein kinase that functions autonomously after Ca(2+)/calmodulin-binding and autophosphorylation, and is involved in sarcoplasmic reticulum Ca(2+) transport in skeletal muscle and may function in dendritic spine and synapse formation and neuronal plasticity (PubMed:16690701). In slow-twitch muscles, is involved in regulation of sarcoplasmic reticulum (SR) Ca(2+) transport and in fast-twitch muscle participates in the control of Ca(2+) release from the SR through phosphorylation of the ryanodine receptor-coupling factor triadin (PubMed:16690701). In the central nervous system, it is involved in the regulation of neurite formation and arborization (PubMed:30184290). It may participate in the promotion of dendritic spine and synapse formation and maintenance of synaptic plasticity which enables long-term potentiation (LTP) and hippocampus-dependent learning. In response to interferon-gamma (IFN-gamma) stimulation, catalyzes phosphorylation of STAT1, stimulating the JAK-STAT signaling pathway (By similarity).

Drugs associated with CAMK2G

SAK-3 (Tohoku University)

Target

CAMK2G x Proteasome x T-type calcium channel

Mechanism

CAMK2G gene stimulants [+2]

Active Org.

Tohoku University

Originator Org.

Tohoku University

Active Indication

Alzheimer Disease

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with CAMK2G

100 Translational Medicine associated with CAMK2G

0 Patents (Medical) associated with CAMK2G

1,298

Literatures (Medical) associated with CAMK2G

01 Dec 2024·Mini-Reviews in Medicinal Chemistry

Therapeutic Potentials of Aconite-like Alkaloids: Bioinformatics and Experimental Approaches

Review

Author: Mares, Catalina ; Buiu, Catalin ; Avram, Speranta ; Staicu, Angela ; Udrea, Ana-Maria

Abstract:Compounds from plants that are used in traditional medicine may have medicinal properties. It is well known that plants belonging to the genus Aconitum are highly poisonous. Utilizing substances derived from Aconitum sp. has been linked to negative effects. In addition to their toxicity, the natural substances derived from Aconitum species may have a range of biological effects on humans, such as analgesic, anti-inflammatory, and anti-cancer characteristics. Multiple in silico, in vitro, and in vivo studies have demonstrated the effectiveness of their therapeutic effects. In this review, the clinical effects of natural compounds extracted from Aconitum sp., focusing on aconitelike alkaloids, are investigated particularly by bioinformatics tools, such as the quantitative structure- activity relationship method, molecular docking, and predicted pharmacokinetic and pharmacodynamic profiles. The experimental and bioinformatics aspects of aconitine’s pharmacogenomic profile are discussed. Our review could help shed light on the molecular mechanisms of Aconitum sp. compounds. The effects of several aconite-like alkaloids, such as aconitine, methyllycacintine, or hypaconitine, on specific molecular targets, including voltage-gated sodium channels, CAMK2A and CAMK2G during anesthesia, or BCL2, BCL-XP, and PARP-1 receptors during cancer therapy, are evaluated. According to the reviewed literature, aconite and aconite derivatives have a high affinity for the PARP-1 receptor. The toxicity estimations for aconitine indicate hepatotoxicity and hERG II inhibitor activity; however, this compound is not predicted to be AMES toxic or an hERG I inhibitor. The efficacy of aconitine and its derivatives in treating many illnesses has been proven experimentally. Toxicity occurs as a result of the high ingested dose; however, the usage of this drug in future research is based on the small quantity of an active compound that fulfills a therapeutic role.

01 Nov 2024·Free Radical Biology and Medicine

CaMKII protein expression and phosphorylation in human skeletal muscle by immunoblotting: Isoform specificity

Article

Author: Martinez-Canton, Miriam ; Garcia-Perez, Giovanni ; Santana, Alfredo ; Calbet, Jose A L ; Galvan-Alvarez, Victor ; Martin-Rincon, Marcos ; Garcia-Gonzalez, Eduardo ; Gallego-Selles, Angel

Calcium (Ca²⁺)/calmodulin-dependent protein kinase II (CaMKII) is activated during exercise by reactive oxygen species (ROS) and Ca²⁺ transients initiating muscle contraction. CaMKII modulates antioxidant, inflammatory, metabolic and autophagy signalling pathways. CaMKII is coded by four homologous genes (α, β, γ, and δ). In rat skeletal muscle, δ_D, δ_A, γ_D, γ_B and β_M have been described while different characterisations of human skeletal muscle CaMKII isoforms have been documented. Precisely discerning between the various isoforms is pivotal for understanding their distinctive functions and regulatory mechanisms in response to exercise and other stimuli. This study aimed to optimize the detection of the different CaMKII isoforms by western blotting using eight different CaMKII commercial antibodies in human skeletal muscle. Exercise-induced posttranslational modifications, i.e. phosphorylation and oxidations, allowed the identification of specific bands by multitargeting them with different antibodies after stripping and reprobing. The methodology proposed has confirmed the molecular weight of β_M CaMKII and allows distinguishing between γ/δ and δ_D CaMKII isoforms. The corresponding molecular weight for the CaMKII isoforms resolved were: δ_D, at 54.2 ± 2.1 kDa; γ/δ, at 59.0 ± 1.2 kDa and 61.6 ± 1.3 kDa; and β_M isoform, at 76.0 ± 1.8 kDa. Some tested antibodies showed high specificity for the δ_D, the most responsive isoform to ROS and intracellular Ca²⁺ transients in human skeletal muscle, while others, despite the commercial claims, failed to show such specificity.

01 Oct 2024·Biochemical and Biophysical Research Communications

Nitric oxide contributes to rapid sclerostin protein loss following mechanical load

Article

Author: Leser, Jenna M ; Buck, Heather V ; Gould, Nicole R ; Ward, Christopher W ; Stains, Joseph P ; Torre, Olivia M

In response to mechanical loading of bone, osteocytes produce nitric oxide (NO•) and decrease sclerostin protein expression, leading to an increase in bone mass. However, it is unclear whether NO• production and sclerostin protein loss are mechanistically linked, and, if so, the nature of their hierarchical relationship within an established mechano-transduction pathway. Prior work showed that following fluid-shear stress (FSS), osteocytes produce NOX2-derived reactive oxygen species, inducing calcium (Ca²⁺) influx. Increased intracellular Ca²⁺ results in calcium-calmodulin dependent protein kinase II (CaMKII) activation, which regulates the lysosomal degradation of sclerostin protein. Here, we extend our discoveries, identifying NO• as a regulator of sclerostin degradation downstream of mechano-activated CaMKII. Pharmacological inhibition of nitric oxide synthase (NOS) activity in Ocy454 osteocyte-like cells prevented FSS-induced sclerostin protein loss. Conversely, short-term treatment with a NO• donor in Ocy454 cells or isolated murine long bones was sufficient to induce the rapid decrease in sclerostin protein abundance, independent of changes in Sost gene expression. Ocy454 cells express all three NOS genes, and transfection with siRNAs targeting eNOS/Nos3 was sufficient to prevent FSS-induced loss of sclerostin protein, while siRNAs targeting iNOS/Nos2 mildly blunted the loss of sclerostin but did not reach statistical significance. Similarly, siRNAs targeting both eNOS/Nos3 and iNOS/Nos2 prevented FSS-induced NO• production. Together, these data show iNOS/Nos2 and eNOS/Nos3 are the primary producers of FSS-dependent NO•, and that NO• is necessary and sufficient for sclerostin protein control. Further, selective inhibition of elements within this sclerostin-controlling mechano-transduction pathway indicated that NO• production occurs downstream of CaMKII activation. Targeting Camk2d and Camk2g with siRNA in Ocy454 cells prevented NO• production following FSS, indicating that CaMKII is needed for NO• production. However, NO• donation (1min) resulted in a significant increase in CaMKII activation, suggesting that NO• may have the ability to tune CaMKII response. Together, these data support that CaMKII is necessary for, and may be modulated by NO•, and that the interaction of these two signals is involved in the control of sclerostin protein abundance, consistent with a role in bone anabolic responses.

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CAMK2G

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