
-   MT2A is up-regulated during oxidative stress and hypoxia/reoxygenation (H/R) with the increasing levels of ROS [PMID: 19433272], H2O2 [PMID: 26101557], and various metal ions, such as Zn2+ and Cu+ [PMID: 23925449]. MT2A has metal-responsive elements (MREs) in its regulatory regions that can bind to metal transcription factors when metal ions such as zinc and copper are abundant. This binding activates gene expression, increasing MT2A production [PMID: 32597135]. Deletion of metallothioneins 1 and 2 results in activation of the Akt pathway and increases in myotube size, in type IIb fiber hypertrophy, and ultimately in muscle strength
-   Metallothionein 2A (MT2A) controls cell proliferation and liver metastasis by controlling the MST1/LATS2/YAP1 signaling pathway in colorectal cancer [PMID: 35642057].

## Summary

MT2A, a gene encoding Metallothionein 2A, is intricately linked to the body's response to skeletal muscle toxicity or disease. When skeletal muscle faces injury or stress, such as contusion, oxidative stress, or hypoxia/reoxygenation, there's an elevation in reactive oxygen species (ROS) and metal ions like zinc and copper. MT2A expression is upregulated in these scenarios due to its metal-responsive elements (MREs) that bind to these elevated metal ions, activating gene expression [CS: 8]. The resultant Metallothionein 2A protein, rich in cysteine, binds these excess heavy metals, particularly zinc and copper [CS: 9]. This binding activity helps to mitigate the toxic effects of high metal ion concentration in cells, reducing cellular damage and aiding in recovery [CS: 8].

In response to skeletal muscle stress or disease, the expression of MT2A is involved in muscle cell growth and survival pathways [CS: 7]. Specifically, the absence or inhibition of MT2A, along with Metallothionein 1, has been shown to activate the Akt pathway [CS: 6]. This pathway is critical for cell survival and growth, and its activation leads to increased muscle fiber size, particularly in type IIb fibers, and enhances muscle strength [CS: 7]. In conditions of muscle stress or atrophy, such as in sarcopenia, MT2A's normal function appears to be a regulatory one, acting as a brake on the Akt pathway and thus on muscle growth [CS: 6]. Therefore, when MT2A is upregulated in response to muscle stress or injury, it may be contributing to a protective mechanism that prevents excessive muscle growth and maintains muscle homeostasis [CS: 6].
