Hussain, M. S. | Search bioRxiv

bioRxiv2020

Identification of radiation responsive proteins from Spleen and Intestine tissue of mice using Mass Spectrometry approach.

PurposeExposure to ionizing radiation (IR) can cause tissue damage, which is difficult to diagnose and treat as no biomarker is available for detection. We aimed to identify proteomic signature of radiation exposure (9.5Gry) in mice and to assess the utility of Podophyllotoxin extract (PTOX) in preventing radiation injury. Materials and MethodsSpleen and Small intestinal (SI) tissues were taken from control and lethally irradiated mice at different time intervals with or without pre-treatment with Podophyllotoxin extract. Proteins were identified using Mass Spectrometry and matched with Peptide Mass Fingerprinting. ResultsWe found multiple differentially expressed radiation responsive proteins from Spleen and SI tissues in irradiated mice at 24 hours and 30 days in comparison to healthy controls (p<0.05). Differentially expressed proteins like Chromosome transmission fidelity factor ano thath 18 homolog (CTF18) and Rho GTPase-activating protein from spleen and Acta_Mouse protein from SI were identified. These proteins disappeared at 48 hrs. after IR, but re-appeared after 13 days and fully recovered at 30 days in Podophyllotoxin treated group. ConclusionsSuch proteins may be useful in early detection of radiation exposure. Pre-treatment with Podophyllotoxin leads to recovery of the disappeared proteins and improved survival following exposure to irradiation.

biochemistry↗

bioRxiv2019

RRP7A links primary microcephaly to radial glial cells and dysfunction of ribosomal biogenesis, neurogenesis and ciliary resorption

Introductory paragraphPrimary microcephaly (MCPH) is characterized by reduced brain size and intellectual disability1. The exact pathophysiological mechanism underlying MCPH remains to be elucidated, but dysfunction of neuronal progenitors in the developing neocortex plays a major role1. Using homozygosity mapping and whole exome sequencing, we identified a homozygous missense mutation (p.W155C) in Ribosomal RNA Processing 7 Homolog A, RRP7A, which segregated with MCPH in a consanguineous family with 10 affected individuals. RRP7A is expressed in neural stem cells/radial glial cells of the developing human forebrain, and targeted mutation of Rrp7a leads to defects in both neurogenesis and proliferation in a mouse stem cell model. RRP7A localizes to centrosomes, cilia and nucleoli, and patient-derived fibroblasts display defects in processing of ribosomal RNA, resorption of primary cilia and cell cycle progression. Finally, analysis of zebrafish embryos with loss-of-function mutation in rrp7a confirmed that RRP7A depletion causes reduced brain size, impaired neurogenesis and cell proliferation as well as defective ribosomal RNA processing. These findings provide novel insight into human brain development and MCPH.

neuroscience↗