Significance of elevated Prohibitin 1 levels in Multiple Sclerosis patients lymphocytes towards the assessment of subclinical disease activity and its role in the central nervous system pathology of disease

Kumar, Madathiparambil Kumaran Satheesh; Nair, Sreepriya; Mony, Ullas; Kalingavarman, Sugavanan; Venkat, Ramaswamynathan; Sivanarayanan, T.B.; Unni, Ayalur Kodakara Kochugovindan; Rajeshkannan, Ramiah; Anandakuttan, Anandakumar; Radhakrishnan, Sureshkumar; Menon, Krishnakumar N.

doi:10.1016/j.ijbiomac.2017.12.061

Cited by 10 publications

(4 citation statements)

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“…This complex is required for OPA1 stability [42], indeed the deletion of PHB2 leads to the impaired cellular proliferation, aberrant mitochondrial cristae morphogenesis, and apoptosis [24,42], while an over-expression of PHB2 is reported to protect cells from apoptosis [43]. We show, according with others [26] and as response to OS [25], a strong increase of PHB2 protein level in MS samples, thus representing another element of resistance to apoptosis. It worth mentioning that an elevated autophagic flux has been reported in autoreactive T cells, both in patients and in the mouse model of experimental autoimmune encephalomyelitis [44].…”

Section: Discussionsupporting

confidence: 81%

“…Evidences indicate that mitochondrial PHB2 is over expressed under conditions of oxidative stress [25]. Interesting, PHB2 has been found up-regulated in lymphocytes of MS patients [26]. OPA1 processing is also modulated by its acetylation status mediated by SIRT3 enzyme, a mitochondrial deacetylase that also plays an important role in apoptosis [20].…”

Section: Introductionmentioning

confidence: 99%

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PBMC of Multiple Sclerosis Patients Show Deregulation of OPA1 Processing Associated with Increased ROS and PHB2 Protein Levels

et al. 2020

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Multiple sclerosis (MS) is an autoimmune disease in which activated lymphocytes affect the central nervous system. Increase of reactive oxygen species (ROS), impairment of mitochondria-mediated apoptosis and mitochondrial alterations have been reported in peripheral lymphocytes of MS patients. Mitochondria-mediated apoptosis is regulated by several mechanisms and proteins. Among others, optic atrophy 1 (OPA1) protein plays a key role in the regulating mitochondrial dynamics, cristae architecture and release of pro-apoptotic factors. Very interesting, mutations in OPA1 gene, have been associated with multiple sclerosis-like disorder. We have analyzed OPA1 and some factors involved in its regulation. Fifteen patients with MS and fifteen healthy control subjects (HC) were enrolled into the study and peripheral blood mononuclear cells (PBMCs) were isolated. H2O2 level was measured spectrofluorimetrically, OPA1, PHB2, SIRT3, and OMA1 were analyzed by western blotting. Statistical analysis was performed using Student’s t-test. The results showed that PBMC of MS patients were characterized by a deregulation of OPA1 processing associated with increased H2O2 production, inactivation of OMA1 and increase of PHB2 protein level. The presented data suggest that the alteration of PHB2, OMA1, and OPA1 processing could be involved in resistance towards apoptosis. These molecular parameters could also be useful to assess disease activity.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

PBMC of Multiple Sclerosis Patients Show Deregulation of OPA1 Processing Associated with Increased ROS and PHB2 Protein Levels

et al. 2020

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“…The anti-apoptotic role of PHBs in mitochondria is underlined by the high level of the PHB complex within mitochondria in cancer cells [16]. Furthermore, PHB1 accumulates in mitochondria of melanoma cells after anticancer treatment, leading to chemoresistance [82], and an elevated PHB1 level is reported in activated lymphocytes, characterized by resistance towards apoptosis, of patients affected by multiple sclerosis [83].…”

Section: Role Of Prohibitins In Apoptosismentioning

confidence: 99%

Prohibitins: A Critical Role in Mitochondrial Functions and Implication in Diseases

Signorile

Sgaramella

Bellomo

et al. 2019

Cells

154

159

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Prohibitin 1 (PHB1) and prohibitin 2 (PHB2) are proteins that are ubiquitously expressed, and are present in the nucleus, cytosol, and mitochondria. Depending on the cellular localization, PHB1 and PHB2 have distinctive functions, but more evidence suggests a critical role within mitochondria. In fact, PHB proteins are highly expressed in cells that heavily depend on mitochondrial function. In mitochondria, these two proteins assemble at the inner membrane to form a supra-macromolecular structure, which works as a scaffold for proteins and lipids regulating mitochondrial metabolism, including bioenergetics, biogenesis, and dynamics in order to determine the cell fate, death, or life. PHB alterations have been found in aging and cancer, as well as neurodegenerative, cardiac, and kidney diseases, in which significant mitochondrial impairments have been observed. The molecular mechanisms by which prohibitins regulate mitochondrial function and their role in pathology are reviewed and discussed herein.

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“…The cytokines IL-6, IL-8, IL-12p70, IP-10, and MCP-1 were quantified simultaneously in aqueous humor samples (50 µL) of DME patients (responders and nonresponders) by using multiplexed human cytometric bead array (CBA) kit[ 16 17 18 ] (Becton Dickinson, San Diego, California). The samples and standards were prepared as per manufacturer's instructions.…”

Section: Methodsmentioning

confidence: 99%

Significance of monitoring vascular endothelial growth factor, monocyte chemoattractant protein-1 and Interleukin-8 in diabetic macular edema towards early identification of nonresponders to ranibizumab therapy

Xavier

Pallikara

Saji

et al. 2021

Indian Journal of Ophthalmology

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Purpose: Identification of nonresponders prior to anti-vascular endothelial growth factor (anti-VEGF) therapy would help in the judicious clinical management of diabetic macular edema (DME) patients. Thus, a systematic study was initiated to identify nonresponding DME patient population undergoing ranibizumab treatment to figure out additional inflammatory components that may contribute to their nonresponsiveness to anti-VEGF therapy. Methods: A total of 40 patients recruited to this investigator-initiated trial received intravitreal ranibizumab monthly for 3 months. The fourth- and fifth-month injections were according to PRN protocol and the sixth-month injection was mandatory. Best-corrected visual acuity (BCVA), central macular thickness (CMT), and VEGF in aqueous humor were measured for all the patients. Patients were grouped into responders/nonresponders on the formulated criteria and the levels of key pro-inflammatory cytokines were also measured between the two groups at baseline, 2 month and 5 months using cytometric bead array (CBA). Results: Eleven patients were categorized (29.72%) as responders and 10 patients (27.02%) as nonresponders. Nonresponders showed poorer BCVA ( P = 0.024, 0.045, and 0.048 for 4, 5, and 6 months) and higher CMT ( P = 0.021, 0.0008 and <0.0001 for baseline, 1, 2, 3, 4, 5, and 6 months) compared to responders. The cytokines IL-8, MCP-1 were significantly up regulated ( P = 0.0048 and 0.029 for MCP-1 and IL-8) in nonresponders. Conclusion: Elevated MCP-1 and IL-8 levels found in the nonresponders could be used as a prognostic marker to identify these groups of patients and can help in developing alternative treatment options along with anti-VEGF therapy.

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Significance of elevated Prohibitin 1 levels in Multiple Sclerosis patients lymphocytes towards the assessment of subclinical disease activity and its role in the central nervous system pathology of disease

Cited by 10 publications

References 38 publications

PBMC of Multiple Sclerosis Patients Show Deregulation of OPA1 Processing Associated with Increased ROS and PHB2 Protein Levels

PBMC of Multiple Sclerosis Patients Show Deregulation of OPA1 Processing Associated with Increased ROS and PHB2 Protein Levels

Prohibitins: A Critical Role in Mitochondrial Functions and Implication in Diseases

Significance of monitoring vascular endothelial growth factor, monocyte chemoattractant protein-1 and Interleukin-8 in diabetic macular edema towards early identification of nonresponders to ranibizumab therapy

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