Under pathological conditions such as inflammation and ischemia-reperfusion injury large amounts of reactive oxygen species (ROS) are generated which, in return, contribute to the development and exacerbation of disease. The second member of the transient receptor potential (TRP) melastatin subfamily, TRPM2, is a Ca²⁺-permeable non-selective cation channel, activated by ROS in an ADP-ribose mediated fashion. In other words, TRPM2 functions as a transducer that converts oxidative stress into Ca²⁺ signaling. There is good evidence that TRPM2 plays an important role in ROS-coupled diseases. For example, in monocytes the influx of Ca²⁺ through TRPM2 activated by ROS contributes to the aggravation of inflammation via chemokine production. In this review, the focus is on TRPM2 as a molecular linker between ROS and Ca²⁺ signaling in ROS-coupled diseases.

A clinical assessment of fungal infection in hepatobiliary and pancreatic diseases during 1975 and 1991 was made and 25 cases of systemic mycosis were noted. Among 25 cases there were 20 liver diseases (hepatocellular carcinoma 12, liver cirrhosis 5, fulminant hepatitis 2, polyarteritis nodosa 1), 2 cases of gallbladder cancer and 3 cases of pancreatic cancer. The fungus was consisted of 14 cases (56%) of Candida, 9 cases of Aspergillus (36%), and 2 cases of Cryptococcus (8%). Fungal infection was most frequent in the lung (8 cases) and esophagus (6 cases), but rarely in the stomach, lymph node, liver, thyroid, kidney and gallbladder. Generalized fungus infection was noted in four cases (16%). Fatal fungal infection was complicated in liver cirrhosis (2 cases), fulminant hepatitis (one case), gallbladder cancer (one case) and cystadenocarcinoma of the pancreas (one case). In five fatal cases three cases of Aspergillus pneumonia and two cases of Candida septicemia were included. Glucocorticoid was used in 13 cases (52%) and anti-cancer drugs was administered in two cases (12%). However, in 9 cases (36%) without treatment of glucocorticoid or anti-cancer drug fungal infection was detected. In conclusion, there is a possibility of fungal infection in grave hepatic diseases and empirical administration of anti-fungal agent may be necessary.

Transient receptor potential melastatin 2 (TRPM2) channel is a Ca²⁺-permeable, redox-activated cardiac ion channel protective in ischemia–reperfusion, but whether it regulates atrial endocrine output under stress is unclear. Here, we investigated whether TRPM2 contributes to the atrial natriuretic peptide (ANP) response during β-adrenergic stimulation. We compared how male C57BL/6J wild-type (WT) and TRPM2 knockout (TRPM2^−/−) mice (8–12 weeks old) respond to β-adrenergic stress induced by isoproterenol (ISO) using echocardiography, histology, RT-PCR, electrophysiology, Ca²⁺ imaging, ELISA, and atrial RNA-seq. We detected abundant Trpm2 transcripts in WT atria and measured ADP-ribose (ADPr)-evoked currents and hydrogen peroxide (H₂O₂)-induced Ca²⁺ influx characteristic of TRPM2; these were absent in TRPM2^−/− cells. Under the ISO-induced hypertrophic model, TRPM2^−/− mice developed greater cardiac hypertrophy, fibrosis, and systolic dysfunction compared with WT mice. Atrial bulk RNA-seq showed significant induction of Nppa (ANP precursor gene) in WT + ISO, accompanied by higher circulating ANP; TRPM2^−/− + ISO showed blunted Nppa and ANP responses. ISO-treated TRPM2^−/− mice exhibited more blunt responses, in both Nppa transcripts and circulating ANP levels. Exogenous ANP attenuated ISO-induced dysfunction, hypertrophy, and fibrosis in TRPM2^−/− mice, suggesting that TRPM2 is needed for the cardioprotective endocrine response via ANP to control stress-induced β-adrenergic remodeling.