Oplah-KO Mouse

OPLAH, encoding for 5-oxoprolinase, is a member of the γ-glutamyl cycle. It functions by scavenging 5-oxoproline, an important mediator of oxidative stress. The γ-glutamyl cycle is involved in glutathione metabolism, which is crucial for maintaining cellular redox balance [3,4].

In Oplah full-body knock-out (KO) mice, higher 5-oxoproline levels coupled with increased oxidative stress were observed. These KO mice had increased cardiac and renal fibrosis, elevated left ventricular filling pressures, impaired LV relaxation, yet a normal LV ejection fraction compared with wild-type littermates. After cardiac ischaemia/reperfusion injury, a higher mortality rate was seen in KO mice. Also, in Chinese hamsters with type 2 diabetes mellitus, downregulation of OPLAH in skeletal muscles was found to affect insulin resistance and glucose uptake. Silencing OPLAH in human skeletal muscle cells increased reactive oxygen species content, decreased GSH content, inhibited the PI3K/Akt/GLUT4 signaling pathway, and reduced glucose uptake [1,2].

In conclusion, OPLAH plays a vital role in maintaining redox balance by regulating 5-oxoproline levels. Studies using Oplah KO mouse models have revealed its significance in heart failure with a preserved ejection fraction and type 2 diabetes mellitus, highlighting its potential as a therapeutic target in these disease areas [1,2,3].