Evaluation of gammah2ax in buccal cells as a molecular biomarker of DNA damage in Alzheimer’s disease in the AIBL study of ageing

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. In response to double-stranded breaks (DSBs) in chromosomal DNA, H2AX (a member of histone H2A family) becomes phosphorylated to form γH2AX. Although increased levels of γH2AX have been reported in the neuronal nuclei of Alzheimer’s disease (AD) patients, the understanding of γH2AX responses in buccal nuclei of individuals with mild cognitive impairment (MCI) and AD remain unexplored. In the current study, endogenous γH2AX was measured in buccal cell nuclei from MCI (n = 18) or AD (n = 16) patients and in healthy controls (n = 17) using laser scanning cytometry (LSC). The γH2AX level was significantly elevated in nuclei of the AD group compared to the MCI and control group, and there was a concomitant increase in P-trend for γH2AX from the control group through MCI to the AD group. Receiver-operating characteristic curves were carried out for different γH2AX parameters; γH2AX in nuclei resulted in the greatest area under the curve value of 0.7794 (p = 0.0062) with 75% sensitivity and 70% specificity for the identification of AD patients from control. In addition, nuclear circularity (a measure of irregular nuclear shape) was significantly higher in the buccal cell nuclei from the AD group compared with the MCI and control groups. Additionally, there was a positive correlation between the nuclear circularity and γH2AX signals. The results indicated that increased DNA damage is associated with AD

Antiarrhythmic mechanisms of omega-3 polyunsaturated fatty acids in rat ventricular cardiomyocytes / Wayne R. Leifert.

Includes bibliographical references (leaves 237-257).xx, 257 leaves : ill. ; 30 cm.Investigates the mechanisms underlying the antiarrhythmic effects of omega-3 polyunsaturated fatty acids using adult rat ventricular cardiac myocytes.Thesis (Ph.D.)--Adelaide University, Dept. of Physiology, 200

γH2AX is a biomarker of modulated cytostatic drug resistance

4 page(s

Antiarrhythmic fatty acids and antioxidants in animal and cell studies

Leifert, Wayne R; Jahangiri, Anisa; McMurchie, Edward J

Membrane fluidity changes are associated with the antiarrhythmic effects of docosahexaenoic acid in adult rat cardiomyocytes

Leifert, Wayne R; Jahangiri, Anisa; McMurchie, Edward

Termination of asynchronous contractile activity in rat atrial myocytes by n-3 polyunsaturated fatty acids

Jahangiri, Anisa; Leifert, Wayne; Patten, Glen; McMurchie, Edwar

Persistent γH2AX : a promising molecular marker of DNA damage and aging

One of the earliest cellular responses to DNA double strand breaks (DSBs) is the phosphorylation of the core histone protein H2AX (termed γH2AX). Persistent γH2AX is the level of γH2AX above baseline, measured at a given time-point beyond which DNA DSBs are normally expected to be repaired (usually persist for days to months). This review summarizes the concept of persistent γH2AX in the context of exogenous source induced DNA DSBs (e.g. ionizing radiation (IR), chemotherapeutic drugs, genotoxic agents), and endogenous γH2AX levels in normal aging and accelerated aging disorders. Summary of the current literature demonstrates the following (i) γH2AX persistence is a common phenomenon that occurs in humans and animals; (ii) nuclei retain persistent γH2AX foci for up to several months after IR exposure, allowing for retrospective biodosimetry; (iii) the combination of various radiosensitizing drugs with ionizing radiation exposure leads to persistent γH2AX response, thus enabling the potential for monitoring cancer patients' response to chemotherapy and radiotherapy as well as tailoring cancer treatments; (iv) persistent γH2AX accumulates in telomeric DNA and in cells undergoing cellular senescence; and (v) increased endogenous γH2AX levels may be associated with diseases of accelerated aging. In summary, measurement of persistent γH2AX could potentially be used as a marker of radiation biodosimetry, evaluating sensitivity to therapeutic genotoxins and radiotherapy, and exploring the association of unrepaired DNA DSBs on telomeres with diseases of accelerated aging.19 page(s

Cardiovascular biology of interleukin-6

IL-6 activates cell surface signalling via the assembly of IL-6, the IL-6 receptor (IL-6R) and the signalling receptor gp130. Assembly of the (hexameric) signalling complex of IL-6, IL-6R and gp130 occurs in a sequential manner and therefore this signalling complex lends itself to several potential sites for drug targeting. This review discusses some of the mechanisms of IL-6 signalling on various aspects of cardiovascular biology as well as some recent developments in drug targeting of this complex.