Derinat Protects Skin against Ultraviolet-B (UVB)-Induced Cellular Damage

Abstract

Ultraviolet-B (UVB) is one of the most cytotoxic and mutagenic stresses that contribute to skin damage and aging through increasing intracellular Ca 2+ and reactive oxygen species (ROS). Derinat (sodium deoxyribonucleate) has been utilized as an immunomodulator for the treatment of ROS-associated diseases in clinics. However, the molecular mechanism by which Derinat protects skin cells from UVB-induced damage is poorly understood. Here, we show that Derinat significantly attenuated UVB-induced intracellular ROS production and decreased DNA damage in primary skin cells. Furthermore, Derinat reduced intracellular ROS, cyclooxygenase-2 (COX-2) expression and DNA damage in the skin of the BALB/c-nu mice exposed to UVB for seven days in vivo. Importantly, Derinat blocked the transient receptor potential canonical (TRPC) channels (TRPCs), as demonstrated by calcium imaging. Together, our results indicate that Derinat acts as a TRPCs blocker to reduce intracellular ROS production and DNA damage upon UVB irradiation. This mechanism provides a potential new application of Derinat for the protection against UVB-induced skin damage and aging.

Nociceptive transient receptor potential canonical 7 (TRPC7) mediates aging‐associated tumorigenesis induced by ultraviolet B

“…Our discovery that TRPC7 is a nociceptive mechanoreceptor, together with our previous finding that TRPC7 has a role in UVB‐induced skin aging via increased ROS production (Hsu et al, ), is consistent with the previously reported links between nociceptive TRP receptors and aging (Buffenstein, ; Park et al, ; Riera et al, ; Seluanov et al, ). Interestingly, TRP channel expression has been previously shown to increase with age‐related degeneration (Santoni & Farfariello, ; Takada et al, ; Yue et al, ), but our results suggest that TRP channels, especially nociceptive TRP channels, are also important in initiating the aging process.…”

“…Furthermore, the knockdown of TRPC7 inhibited UVB‐induced p53 expression in keratinocytes (Figure e–g), which was corroborated by our observation that the UVB‐induced activation of the p53 pathway was reduced in TRPC7 +/− and TRPC7 −/− mice (Figure i). In addition, extracellular Ca 2+ influx is known to induce cyclooxygenase‐2 (COX‐2) expression, which increases p53 pathway activation and promotes the aging process (Hsu et al, ; Kim et al, ). We found that after UVB exposure, the high levels of COX‐2 protein expression observed in the epidermis of wild‐type mice were decreased to minimal levels in TRPC7 +/− and TRPC7 −/− mice (Figure h).…”

“…In this study, we show evidence for a role of TRPC7 as a potential tumor initiator gene in UVB‐induced epidermal aging and skin tumorigenesis. After UVB irradiation, the increased level of diacylglycerol in the cell membrane immediately activates TRPC7 (Hsu et al, ), and increased Ca 2+ influx from TRPC7 in turn further upregulates TRPC7 levels (Figure e). Several Ca 2+ ‐dependent transcription factors, such as nuclear factor (NF)‐κB, cAMP response element binding protein, and nuclear factor of activated T cells protein may be involved in controlling TRPC7 upregulation to amplify its activation.…”

“…Recently, we showed that TRPC7 is involved in ultraviolet B (UVB)‐induced skin aging and diacylglycerol production in the cytoplasmic membrane and that this skin aging could be prevented by attenuating the UVB‐induced elevation of intracellular Ca 2+ concentration ([Ca 2+ ] i ; Hsu et al, ). The only other known physiologic function of TRPC7 reported to date is its role in the initiation of seizure activity (Phelan, Shwe, Abramowitz, Birnbaumer, & Zheng, ).…”

Immune-metabolic genesis of pathological processes

“…Thymomimetic agents turned out to be lipid metabolism regulators, reduced blood glucose levels, and normalized liver function indicators. In patients with chronic pyelonephritis, galavit resulted in the normalization of creatinine and bilirubin; super lymph -creatinine; derinat -urea, creatinine, ALAT and ASAT (Hsu et al 2015). Nucleic acid preparations -sodium nucleinate, ridostin, derinat, poludan, isoprinosine -manifested not only differentiated immunocorrective, but also metabolic effects (Daniels et al 2018).…”