Proteomic analysis of the effects of caffeine in a neonatal rat model of hypoxic‐ischemic white matter damage

Abstract

Aim White matter damage (WMD) is the main cause of cerebral palsy and cognitive impairment in premature infants. Although caffeine has been shown to possess neuroprotective effects in neonatal rats with hypoxic‐ischemic WMD, the mechanisms underlying these protective effects are unclear. Herein, proteins modulated by caffeine in neonatal rats with hypoxic‐ischemic WMD were evaluated. Methods We identified differential proteins and performed functional enrichment analyses between the Sham, hypoxic‐ischemic WMD (HI), and HI+caffeine‐treated WMD (Caffeine) groups. Confirmed the changes and effect of proteins in animal models and determined cognitive impairment via water maze experiments. Results In paraventricular tissue, 47 differential proteins were identified between the Sham, HI, and Caffeine groups. Functional enrichment analyses showed that these proteins were related to myelination and axon formation. In particular, the myelin basic protein (MBP), proteolipid protein, myelin‐associated glycoprotein precursor, and sirtiun 2 (SIRT2) levels were reduced in the hypoxic‐ischemic WMD group, and this effect could be prevented by caffeine. Caffeine alleviated the hypoxic‐ischemic WMD‐induced cognitive impairment and improved MBP, synaptophysin, and postsynaptic density protein 95 protein levels after hypoxic‐ischemic WMD by preventing the HI‐induced downregulation of SIRT2; these effects were subsequently attenuated by the SIRT2 inhibitor AK‐7. Conclusion Caffeine may have clinical applications in the management of prophylactic hypoxic‐ischemic WMD; its effects may be mediated by proteins related to myelin development and synapse formation through SIRT2.

Early versus late caffeine and/or non‐steroidal anti‐inflammatory drugs (NSAIDS) for prevention of intermittent hypoxia‐induced neuroinflammation in the neonatal rat

“…In our study, early Ibu in RA as well as Caff in hyperoxia seemed to favor myelination, while late treatment caused reduced myelination (data not shown). The protective effect of Caff on HIE‐induced WM damage was shown in neonatal rats (Yang et al, 2022), consistent with our findings. Overall, IH seems to negatively affect the process of myelination regardless of early or late treatment.…”

Concentration-Dependent Investigation of the Inhibition of Bromelain Mediated Protein Hydrolysis on Egg Albumen through Coffea arabica

“…Moreover, this non-linear relationship between caffeine concentration and its impact on protein hydrolysis may be indicative of the complex pharmacokinetic interactions of caffeine with enzymes, affecting their activity and leading to pharmacokinetic interactions with medications and other compounds (Romero-Martínez et al, 2021; Rasmussen et al, 1998). Additionally, the inhibitory effect of caffeine on speci c enzymes has been explored in different biological systems, highlighting its potential as an enzyme inhibitor in various contexts (Liu et al, 2022;Selby & Sancar, 1990). Furthermore, the non-linear relationship between caffeine concentration and protein hydrolysis may be in uenced by the diverse physiological effects of caffeine.…”

TRIM67 alleviates cerebral ischemia‒reperfusion injury by protecting neurons and inhibiting neuroinflammation via targeting IκBα for K63-linked polyubiquitination

“…They specifically target RIG-I or TAB2 for K63-linked polyubiquitination, promoting RIG-I or TAB2-mediated NF-κB activation. More notably, prior research revealed that TRIM67 was markedly decreased after ischemic stroke [ 27 ] and could inhibit NF-κB activation and lessen the release of inflammatory components, hence having a certain anti-inflammatory impact [ 26 ]. The probable mechanism of TRIM67 was investigated by specifically targeting IκBα, a crucial negative regulator of NF-κB signaling.…”

“…A previous study claimed that TRIM67 inhibits TNFα-triggered activation by competitively binding β-TrCP to IκBα [ 26 ]. Meanwhile, proteomic analysis found that TRIM67 expression dramatically decreases following stroke [ 27 ], implying that it might be involved in ischemic stroke. However, the significance and underlying mechanisms of NF-κB regulation of TRIM67 are not fully understood in ischemic stroke.…”