
-   In dystrophic muscle fibers, disruptions in calcium signaling negatively impact muscle function, contributing to increased CA-III levels. Carbonic anhydrase III (CAIII) is highly expressed in slow-twitch myofibers in skeletal muscle. The fast-twitch to slow-twitch transformation of myofibers following denervation is accompanied by increased CAIII expression, suggesting that the effects of nerve impulses on skeletal-muscle remodeling influence CAIII expression. Skeletal muscle [Ca2+]i altered CAIII expression. The myocyte enhancer factor 2C (MEF2C) was identified as the key transcription factor regulating [Ca2+]i-mediated changes in CAIII transcription. MEF2C interaction and direct binding of the CAIII promoter between -416 and -200 base pair. Investigations of upstream cytoplasmic signaling pathways responsible for MEF2C activation revealed Ca2+/calmodulin-dependent protein kinase II (CaMKII) as the key factor involved in MEF2C-mediated regulation of CAIII expression. This study demonstrates that the Ca2+-CaMKII-MEF2C signaling pathway is the key factor involved in regulating CAIII expression in skeletal muscle [PMID: 31614133].

## Summary

CA3 dysregulation in bone marrow diseases and toxicities can be explained through its established functions and responses to cellular stress [CS: 8]. CA3, as a carbonic anhydrase, is involved in the reversible hydration of carbon dioxide, aiding in maintaining cellular pH balance and ion transport [CS: 10]. In the context of bone marrow, where rapid cell division and metabolism occur, maintaining pH homeostasis is crucial [CS: 9]. When bone marrow cells are exposed to toxic events like oxidative stress or hypoxic conditions, they require efficient mechanisms to manage the altered pH and ionic environment [CS: 8].

The upregulation of CA3 in response to hypoxia, as indicated by its hypoxia-responsive expression, suggests a protective mechanism against acidic conditions often associated with low oxygen levels [CS: 7]. This aligns with CA3's role in converting CO2 to bicarbonate ions, thus counteracting acidosis [CS: 9]. Similarly, the increased expression of CA3 in conditions of oxidative stress, as seen in Evi1-associated repression of CA3 leading to increased apoptosis, underscores CA3's role in cellular defense [CS: 6]. By facilitating the rapid conversion of CO2, a byproduct of cellular metabolism, to less harmful bicarbonate, CA3 might help in mitigating the effects of oxidative stress, thereby promoting cell survival in the bone marrow during toxic events [CS: 8].
