Molecular Basis of Sex Difference in Neuroprotection induced by Hypoxia Preconditioning in Zebrafish

Abstract

Hypoxia, the major cause of ischemia, leads to debilitating disease in infants via birth asphyxia and cerebral palsy, whereas in adults via heart attack and stroke. A widespread, natural protective phenomenon termed 'Hypoxic Preconditioning' occurs when prior exposures to hypoxia eventually results in robust hypoxia resistance. Accordingly, we have developed a novel model of sex-specific hypoxic preconditioning in adult zebrafish to mimic the tolerance of mini stroke(s) in human, which appears to protect against the severe damage inflicted by a major stroke event. Remarkable difference in the progression pattern of neuroprotection between preconditioning hypoxia followed by acute hypoxia (PH) group, and acute hypoxia (AH) group were observed with noticeable sex difference. Since gender difference has been reported in stroke, it was pertinent to investigate whether any such sex difference also exists in PH's protective mechanism against acute ischemic stroke. In order to elucidate the neural molecular mechanisms behind sex difference in neuroprotection induced by PH, a high throughput proteomics approach utilizing iTRAQ was performed, followed by protein enrichment analysis

Hypoxia inducible factors regulate hepatitis B virus replication by activating the basal core promoter

“…Estrogen signaling was reported to inhibit both HIF-1α transcriptional activity [42] and HBV transcription [43,44], providing a potential explanation for the sex-dependent differences noted in our model. A recent in depth proteomic study investigating the molecular basis of sex difference in zebrafish response to hypoxia preconditioning identified a complex network of signalling pathways [45]. Hypoxic gene expression and HBV RNA levels in our CHB samples were independent of sex, however, this may reflect the post-menopausal age of females in our small cohort and is worthy of further investigation.…”